Novel non‑metal‑based contrast agents for MR imaging: Emerging approaches and clinical perspectives (Review)

Du,Taoming; Luo,Haiyang; Song,Huizhen; Lin,Tao; Yu,Qin

doi:10.3892/ijo.2025.5776

Novel non‑metal‑based contrast agents for MR imaging: Emerging approaches and clinical perspectives (Review)

Authors:
- Taoming Du
- Haiyang Luo
- Huizhen Song
- Tao Lin
- Qin Yu
View Affiliations

Affiliations: Department of Radiology, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan 610213, P.R. China
Published online on: July 15, 2025 https://doi.org/10.3892/ijo.2025.5776
Article Number: 70
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Magnetic Resonance Imaging (MRI) relies on contrast agents to enhance image quality and diagnostic accuracy. Traditional metal‑based agents, such as gadolinium compounds, raise safety concerns due to potential toxicity and long‑term retention in the body. The present review examines recent advancements in non‑metal‑based MRI contrast agents, focusing on fluorine‑19 (19F) compounds, chemical exchange saturation transfer (CEST) agents, nitroxide radicals, and hyperpolarized carbon agents. It discussed the mechanisms by which these agents improve contrast, including their biocompatibility and ability to provide molecular and metabolic information. Key findings highlight the high specificity of19F agents due to negligible background signals, the capacity of CEST agents for molecular imaging without metals, nitroxide radicals' utility in redox‑sensitive imaging, and hyperpolarized ¹³C compounds' role in real‑time metabolic assessment. Despite challenges such as low sensitivity and technical complexities, these non‑metal‑based agents offer promising, safer alternatives with enhanced diagnostic capabilities, paving the way for more precise and personalized medical imaging.

View Figures

View References

1	Wahsner J, Gale EM, Rodríguez-Rodríguez A and Caravan P: Chemistry of MRI contrast agents: Current challenges and new frontiers. Chem Rev. 119:957–1057. 2019. View Article : Google Scholar :
2	Pollack A, Kontorovich AR, Fuster V and Dec GW: Viral myocarditis-diagnosis, treatment options, and current controversies. Nat Rev Cardiol. 12:670–680. 2015. View Article : Google Scholar : PubMed/NCBI
3	Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L, Rovira A, Sastre-Garriga J, Tintorè M, Frederiksen JL, et al: MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 15:292–303. 2016. View Article : Google Scholar : PubMed/NCBI
4	Wattjes MP, Rovira À, Miller D, Yousry TA, Sormani MP, de Stefano MP, Tintoré M, Auger C, Tur C, Filippi M, et al: Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis-establishing disease prognosis and monitoring patients. Nat Rev Neurol. 11:597–606. 2015. View Article : Google Scholar : PubMed/NCBI
5	Bitar R, Leung G, Perng R, Tadros S, Moody AR, Sarrazin J, McGregor C, Christakis M, Symons S, Nelson A and Roberts TP: MR pulse sequences: What every radiologist wants to know but is afraid to ask. Radiographics. 26:513–537. 2006. View Article : Google Scholar : PubMed/NCBI
6	Villaraza AJL, Bumb A and Brechbiel MW: Macromolecules, dendrimers, and nanomaterials in magnetic resonance imaging: The interplay between size, function, and pharmacokinetics. Chem Rev. 110:2921–2959. 2010. View Article : Google Scholar : PubMed/NCBI
7	Angelovski G: Heading toward macromolecular and nanosized bioresponsive MRI probes for successful functional imaging. Acc Chem Res. 50:2215–2224. 2017. View Article : Google Scholar : PubMed/NCBI
8	Sun C, Lin H, Gong X, Yang Z, Mo Y, Chen X and Gao J: DOTA-branched organic frameworks as giant and potent metal chelators. J Am Chem Soc. 142:198–206. 2020. View Article : Google Scholar
9	Lanza GM, Winter PM, Neubauer AM, Caruthers SD, Hockett FD and Wickline SA: 1H/19F magnetic resonance molecular imaging with perfluorocarbon nanoparticles. Curr Top Dev Biol. 70:57–76. 2005. View Article : Google Scholar : PubMed/NCBI
10	Jahromi AH, Wang C, Adams SR, Zhu W, Narsinh K, Xu H, Gray DL, Tsien RY and Ahrens ET: Fluorous-soluble metal chelate for sensitive fluorine-19 magnetic resonance imaging nanoemulsion probes. ACS Nano. 13:143–151. 2019. View Article : Google Scholar :
11	Davies GL, Kramberger I and Davis JJ: Environmentally responsive MRI contrast agents. Chem Commun (Camb). 49:9704–9721. 2013. View Article : Google Scholar : PubMed/NCBI
12	Major JL and Meade TJ: Bioresponsive, cell-penetrating, and multimeric MR contrast agents. Acc Chem Res. 42:893–903. 2009. View Article : Google Scholar : PubMed/NCBI
13	Zhou Z and Lu ZR: Gadolinium-based contrast agents for magnetic resonance cancer imaging. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 5:1–18. 2013. View Article : Google Scholar
14	Li Y, Yu H, Qian Y, Hu J and Liu S: Amphiphilic star copolymer-based bimodal fluorogenic/magnetic resonance probes for concomitant bacteria detection and inhibition. Adv Mater. 26:6734–6741. 2014. View Article : Google Scholar : PubMed/NCBI
15	Hu X, Liu G, Li Y, Wang X and Liu S: Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals. J Am Chem Soc. 137:362–368. 2015. View Article : Google Scholar
16	Perazella MA: Current status of gadolinium toxicity in patients with kidney disease. Clin J Am Soc Nephrol. 4:461–469. 2009. View Article : Google Scholar : PubMed/NCBI
17	Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, Haruyama T, Kitajima K and Furui S: Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 276:228–232. 2015. View Article : Google Scholar : PubMed/NCBI
18	Bouvain P, Temme S and Flögel U: Hot spot ¹⁹ F magnetic resonance imaging of inflammation. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 12:e16392020. View Article : Google Scholar
19	Srivastava AK, Kadayakkara DK, Bar-Shir A, Gilad AA, McMahon MT and Bulte JW: Advances in using MRI probes and sensors for in vivo cell tracking as applied to regenerative medicine. Dis Model Mech. 8:323–336. 2015. View Article : Google Scholar : PubMed/NCBI
20	Shen Z, Wu A and Chen X: Iron oxide nanoparticle based contrast agents for magnetic resonance imaging. Mol Pharm. 14:1352–1364. 2017. View Article : Google Scholar
21	Cromer Berman SM, Walczak P and Bulte JW: Tracking stem cells using magnetic nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 3:343–355. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ribot E and Foster P: In vivo MRI discrimination between live and lysed iron-labelled cells using balanced steady state free precession. Eur Radiol. 22:2027–2034. 2012. View Article : Google Scholar : PubMed/NCBI
23	Gawel AM, Betkowska A, Gajda E, Godlewska M and Gawel D: Current non-metal nanoparticle-based therapeutic approaches for glioblastoma treatment. Biomedicines. 12:18222024. View Article : Google Scholar : PubMed/NCBI
24	Lin H, Tang X, Li A and Gao J: Activatable ¹⁹ F MRI nanoprobes for visualization of biological targets in living subjects. Adv Mater. 33:20056572021. View Article : Google Scholar
25	Tirotta I, Dichiarante V, Pigliacelli C, Cavallo G, Terraneo G, Bombelli FB, Metrangolo P and Resnati G: (19)F magnetic resonance imaging (MRI): From design of materials to clinical applications. Chem Rev. 115:1106–1129. 2015. View Article : Google Scholar
26	Xiang Y, Zheng G, Liang Z, Jin Y, Liu X, Chen S, Zhou K, Zhu J, Lin M, He H, et al: Visualizing the growth process of sodium microstructures in sodium batteries by in-situ ²³Na MRI and NMR spectroscopy. Nat Nanotechnol. 15:883–890. 2020. View Article : Google Scholar : PubMed/NCBI
27	Zhou Z, Deng H, Yang W, Wang Z, Lin L, Munasinghe J, Jacobson O, Liu Y, Tang L, Ni Q, et al: Early stratification of radiotherapy response by activatable inflammation magnetic resonance imaging. Nat Commun. 11:30322020. View Article : Google Scholar : PubMed/NCBI
28	Cametti M, Crousse B, Metrangolo P, Milani R and Resnati G: The fluorous effect in biomolecular applications. Chem Soc Rev. 41:31–42. 2012. View Article : Google Scholar
29	Li A, Tang X, Gong X, Chen H, Lin H and Gao J: A fluorinated bihydrazide conjugate for activatable sensing and imaging of hypochlorous acid by ¹⁹F NMR/MRI. Chem Commun (Camb). 55:12455–12458. 2019. View Article : Google Scholar : PubMed/NCBI
30	Chirizzi C, De Battista D, Tirotta I, Metrangolo P, Comi G, Bombelli FB and Chaabane L: Multispectral MRI with dual fluorinated probes to track mononuclear cell activity in mice. Radiology. 291:351–357. 2019. View Article : Google Scholar : PubMed/NCBI
31	Pippard BJ, Neal MA, Maunder AM, Hollingsworth KG, Biancardi A, Lawson RA, Fisher H, Matthews JNS, Simpson AJ, Wild JM and Thelwall PE: Reproducibility of ¹⁹ F-MR ventilation imaging in healthy volunteers. Magn Reson Med. 85:3343–3352. 2021. View Article : Google Scholar : PubMed/NCBI
32	Zhang C, Yan K, Fu C, Peng H, Hawker CJ and Whittaker AK: Biological utility of fluorinated compounds: From materials design to molecular imaging, therapeutics and environmental remediation. Chem Rev. 122:167–208. 2022. View Article : Google Scholar
33	Maxouri O, Bodalal Z, Daal M, Rostami S, Rodriguez I, Akkari L, Srinivas M, Bernards R and Beets-Tan R: How to 19F MRI: applications, technique, and getting started. BJR Open. 5:202300192023.PubMed/NCBI
34	Yu W, Yang Y, Bo S, Li Y, Chen S, Yang Z, Zheng X, Jiang ZX and Zhou X: Design and synthesis of fluorinated dendrimers for sensitive (19)F MRI. J Org Chem. 80:4443–4449. 2015. View Article : Google Scholar : PubMed/NCBI
35	Mehta VD, Kulkarni PV, Mason RP, Constantinescu A and Antich PP: Fluorinated proteins as potential 19F magnetic resonance imaging and spectroscopy agents. Bioconjug Chem. 5:257–261. 1994. View Article : Google Scholar : PubMed/NCBI
36	Couch MJ, Ball IK, Li T, Fox MS, Littlefield SL, Biman B and Albert MS: Pulmonary ultrashort echo time 19F MR imaging with inhaled fluorinated gas mixtures in healthy volunteers: Feasibility. Radiology. 269:903–909. 2013. View Article : Google Scholar : PubMed/NCBI
37	Gutberlet M, Kaireit TF, Voskrebenzev A, Lasch F, Freise J, Welte T, Wacker F, Hohlfeld JM and Vogel-Claussen J: Free-breathing dynamic ¹⁹F gas MR imaging for mapping of regional lung ventilation in patients with COPD. Radiology. 286:1040–1051. 2018. View Article : Google Scholar
38	Xie D, Yu M, Kadakia RT and Que EL: ¹⁹F magnetic resonance activity-based sensing using paramagnetic metals. Acc Chem Res. 53:2–10. 2020. View Article : Google Scholar
39	Jirak D, Galisova A, Kolouchova K, Babuka D and Hruby M: Fluorine polymer probes for magnetic resonance imaging: Quo vadis? MAGMA. 32:173–185. 2019. View Article : Google Scholar :
40	Ruiz-Cabello J, Barnett BP, Bottomley PA and Bulte JWM: Fluorine (19F) MRS and MRI in biomedicine. NMR Biomed. 24:114–129. 2011. View Article : Google Scholar :
41	Peterson KL, Srivastava K and Pierre VC: Fluorinated paramagnetic complexes: Sensitive and responsive probes for magnetic resonance spectroscopy and imaging. Front Chem. 6:1602018. View Article : Google Scholar : PubMed/NCBI
42	Ahrens ET and Bulte JW: Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol. 13:755–763. 2013. View Article : Google Scholar : PubMed/NCBI
43	O'Hagan D: Understanding organofluorine chemistry. An introduction to the C-F bond. Chem Soc Rev. 37:308–319. 2008. View Article : Google Scholar : PubMed/NCBI
44	Bona BL, Koshkina O, Chirizzi C, Dichiarante V, Metrangolo P and Baldelli Bombelli F: Multibranched-based fluorinated Materials: Tailor-made design of ¹⁹F-MRI probes. Acc Mater Res. 4:71–85. 2022. View Article : Google Scholar
45	Bouvain P, Flocke V, Krämer W, Schubert R, Schrader J, Flögel U and Temme S: Dissociation of ¹⁹F and fluorescence signal upon cellular uptake of dual-contrast perfluorocarbon nanoemulsions. MAGMA. 32:133–145. 2019. View Article : Google Scholar
46	Hertlein T, Sturm V, Kircher S, Basse-Lüsebrink T, Haddad D, Ohlsen K and Jakob P: Visualization of abscess formation in a murine thigh infection model of Staphylococcus aureus by 19F-magnetic resonance imaging (MRI). PLoS One. 6:e182462011. View Article : Google Scholar : PubMed/NCBI
47	Flögel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C, Schubert R and Schrader J: In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation. 118:140–148. 2008. View Article : Google Scholar : PubMed/NCBI
48	Balducci A, Helfer BM, Ahrens ET, O'Hanlon CF III and Wesa AK: Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI). J Inflamm (Lond). 9:242012. View Article : Google Scholar : PubMed/NCBI
49	De Vries IJM, Lesterhuis WJ, Barentsz JO, Verdijk P, van Krieken JH, Boerman OC, Oyen WJ, Bonenkamp JJ, Boezeman JB, Adema GJ, et al: Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol. 23:1407–1413. 2005. View Article : Google Scholar : PubMed/NCBI
50	Tang X, Gong X, Li A, Lin H, Peng C, Zhang X, Chen X and Gao J: Cascaded multiresponsive self-assembled ¹⁹F MRI nanoprobes with redox-triggered activation and NIR-induced amplification. Nano Lett. 20:363–371. 2020. View Article : Google Scholar
51	Shin SH, Park SH, Kang SH, Kim SW, Kim M and Kim D: Fluorine-19 magnetic resonance imaging and positron emission tomography of tumor-associated macrophages and tumor metabolism. Contrast Media Mol Imaging. 2017:48963102017. View Article : Google Scholar
52	Fan X, River JN, Muresan AS, Popescu C, Zamora M, Culp RM and Karczmar GS: MRI of perfluorocarbon emulsion kinetics in rodent mammary tumours. Phys Med Biol. 51:211–220. 2006. View Article : Google Scholar : PubMed/NCBI
53	Bae PK, Jung J, Lim SJ, Kim D, Kim SK and Chung BH: Bimodal perfluorocarbon nanoemulsions for nasopharyngeal carcinoma targeting. Mol Imaging Biol. 15:401–410. 2013. View Article : Google Scholar : PubMed/NCBI
54	Helfer BM, Balducci A, Sadeghi Z, O'Hanlon C, Hijaz A, Flask CA and Wesa A: ¹⁹F MRI tracer preserves in vitro and in vivo properties of hematopoietic stem cells. Cell Transplant. 22:87–97. 2013. View Article : Google Scholar
55	Solanki YS, Agarwal M, Gupta A, Gupta S and Shukla P: Fluoride occurrences, health problems, detection, and remediation methods for drinking water: A comprehensive review. Sci Total Environ. 807:1506012022. View Article : Google Scholar
56	Bi J, Mo C, Li S, Huang M, Lin Y, Yuan P, Liu Z, Jia B and Xu S: Immunotoxicity of metal and metal oxide nanoparticles: From toxic mechanisms to metabolism and outcomes. Biomater Sci. 11:4151–4183. 2023. View Article : Google Scholar : PubMed/NCBI
57	De A, Jee JP and Park YJ: Why perfluorocarbon nanoparticles encounter bottlenecks in clinical translation despite promising oxygen carriers? Eur J Pharm Biopharm. 199:1142922024. View Article : Google Scholar : PubMed/NCBI
58	Mohanto N, Mondal H, Park YJ and Jee JP: Therapeutic delivery of oxygen using artificial oxygen carriers demonstrates the possibility of treating a wide range of diseases. J Nanobiotechnology. 23:252025. View Article : Google Scholar : PubMed/NCBI
59	Jennings LE and Long NJ: 'Two is better than one'-probes for dual-modality molecular imaging. Chem Commun (Camb). 3511–3524. 2009. View Article : Google Scholar
60	Lee DE, Koo H, Sun IC, Ryu JH, Kim K and Kwon IC: Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem Soc Rev. 41:2656–2672. 2012. View Article : Google Scholar
61	Jacoby C, Temme S, Mayenfels F, Benoit N, Krafft MP, Schubert R, Schrader J and Flögel U: Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: Image reconstruction, biological half-lives and sensitivity. NMR Biomed. 27:261–271. 2014. View Article : Google Scholar
62	Kaneda MM, Caruthers S, Lanza GM and Wickline SA: Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics. Ann Biomed Eng. 37:1922–1933. 2009. View Article : Google Scholar : PubMed/NCBI
63	Srinivas M, Cruz LJ, Bonetto F, Heerschap A, Figdor CG and De Vries IJM: Customizable, multi-functional fluorocarbon nanoparticles for quantitative in vivo imaging using 19F MRI and optical imaging. Biomaterials. 31:7070–7077. 2010. View Article : Google Scholar : PubMed/NCBI
64	Jiang Z, Liu X, Jeong E and Yu Y: Symmetry-guided design and fluorous synthesis of a stable and rapidly excreted imaging tracer for 19F MRI. Angew Chem Int Ed. 121:4849–4852. 2009. View Article : Google Scholar
65	Li D, Yang J, Xu Z, Li Y, Sun Y, Wang Y, Zou H, Wang K, Yang L, Wu L and Sun X: c-Met-targeting 19F MRI nanoparticles with ultralong tumor retention for precisely detecting small or Ill-defined colorectal liver metastases. Int J Nanomedicine. 18:2181–2196. 2023. View Article : Google Scholar :
66	Zambito G, Deng S, Haeck J, Gaspar N, Himmelreich U, Censi R, Löwik C, Di Martino P and Mezzanotte L: Fluorinated PLGA-PEG-mannose nanoparticles for tumor-associated macrophage detection by optical imaging and MRI. Front Med (Lausanne). 8:7123672021. View Article : Google Scholar : PubMed/NCBI
67	Janjic JM, Srinivas M, Kadayakkara DKK and Ahrens ET: Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection. J Am Chem Soc. 130:2832–2841. 2008. View Article : Google Scholar : PubMed/NCBI
68	Mignion L, Magat J, Schakman O, Marbaix E, Gallez B and Jordan BF: Hexafluorobenzene in comparison with perfluoro-15-crown-5-ether for repeated monitoring of oxygenation using 19F MRI in a mouse model. Magn Reson Med. 69:248–254. 2013. View Article : Google Scholar
69	Heaton AR, Lechuga LM, Tangsangasaksri M, Ludwig KD, Fain SB and Mecozzi S: A stable, highly concentrated fluorous nanoemulsion formulation for in vivo cancer imaging via 19F-MRI. NMR Biomed. 37:e51002024. View Article : Google Scholar :
70	Helfer BM, Balducci A, Nelson AD, Janjic JM, Gil RR, Kalinski P, de Vries IJ, Ahrens ET and Mailliard RB: Functional assessment of human dendritic cells labeled for in vivo (19) F magnetic resonance imaging cell tracking. Cytotherapy. 12:238–250. 2010. View Article : Google Scholar : PubMed/NCBI
71	Vu-Quang H, Vinding MS, Nielsen T, Ullisch MG, Nielsen NC and Kjems J: Theranostic tumor targeted nanoparticles combining drug delivery with dual near infrared and ¹⁹F magnetic resonance imaging modalities. Nanomedicine. 12:1873–1884. 2016. View Article : Google Scholar : PubMed/NCBI
72	Diou O, Tsapis N, Giraudeau C, Valette J, Gueutin C, Bourasset F, Zanna S, Vauthier C and Fattal E: Long-circulating perfluorooctyl bromide nanocapsules for tumor imaging by 19FMRI. Biomaterials. 33:5593–5602. 2012. View Article : Google Scholar : PubMed/NCBI
73	Boissenot T, Fattal E, Bordat A, Houvenagel S, Valette J, Chacun H, Gueutin C and Tsapis N: Paclitaxel-loaded PEGylated nanocapsules of perfluorooctyl bromide as theranostic agents. Eur J Pharm Biopharm. 108:136–144. 2016. View Article : Google Scholar : PubMed/NCBI
74	Łopuszyńska N and Węglarz WP: Contrasting Properties of polymeric nanocarriers for MRI-guided drug delivery. Nanomaterials (Basel). 13:21632023. View Article : Google Scholar : PubMed/NCBI
75	Giraudeau C, Flament J, Marty B, Boumezbeur F, Mériaux S, Robic C, Port M, Tsapis N, Fattal E, Giacomini E, et al: A new paradigm for high-sensitivity 19F magnetic resonance imaging of perfluorooctylbromide. Magn Reson Med. 63:1119–1124. 2010. View Article : Google Scholar : PubMed/NCBI
76	Quang HV, Chang CC, Song P, Hauge EM and Kjems J: Caveolae-mediated mesenchymal stem cell labelling by PSS-coated PLGA PFOB nano-contrast agent for MRI. Theranostics. 8:2657–2671. 2018. View Article : Google Scholar : PubMed/NCBI
77	Gao W and Liang L: Effect of polysaccharide sulfate-loaded poly (lactic-co-glycolic acid) nanoparticles on coronary microvascular dysfunction of diabetic cardiomyopathy. J Biomed Nanotechnol. 18:446–452. 2022. View Article : Google Scholar : PubMed/NCBI
78	A R, Wang H, Nie C, Han Z, Zhou M, Atinuke OO, Wang K, Wang X, Liu S, Zhao J, et al: Glycerol-weighted chemical exchange saturation transfer nanoprobes allow ¹⁹F^/1H dual-modality magnetic resonance imaging-guided cancer radiotherapy. Nat Commun. 14:66442023. View Article : Google Scholar
79	Ahrens ET, Flores R, Xu H and Morel PA: In vivo imaging platform for tracking immunotherapeutic cells. Nat Biotechnol. 23:983–987. 2005. View Article : Google Scholar : PubMed/NCBI
80	Srinivas M, Turner MS, Janjic JM, Morel PA, Laidlaw DH and Ahrens ET: In vivo cytometry of antigen-specific t cells using 19F MRI. Magn Reson Med. 62:747–753. 2009. View Article : Google Scholar : PubMed/NCBI
81	Srinivas M, Morel PA, Ernst LA, Laidlaw DH and Ahrens ET: Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med. 58:725–734. 2007. View Article : Google Scholar : PubMed/NCBI
82	Zhang C, Sanchez RJP, Fu C, Clayden-Zabik R, Peng H, Kempe K and Whittaker AK: Importance of thermally induced aggregation on ¹⁹F magnetic resonance imaging of perfluoropolyether-based comb-shaped poly (2-oxazoline)s. Biomacromolecules. 20:365–374. 2019. View Article : Google Scholar
83	Kolouchova K, Groborz O, Slouf M, Herynek V, Parmentier L, Babuka D, Cernochova Z, Koucky F, Sedlacek O, Hruby M, et al: Thermoresponsive triblock copolymers as widely applicable ¹⁹F magnetic resonance imaging tracers. Chem of Mater. 34:10902–10916. 2022. View Article : Google Scholar
84	Wang Y, Tan X, Usman A, Zhang Y, Sawczyk M, Král P, Zhang C and Whittaker AK: Elucidating the impact of hydrophilic segments on ¹⁹F MRI sensitivity of fluorinated block copolymers. ACS Macro Lett. 11:1195–1201. 2022. View Article : Google Scholar : PubMed/NCBI
85	Nakamura T, Matsushita H, Sugihara F, Yoshioka Y, Mizukami S and Kikuchi K: Activatable 19F MRI nanoparticle probes for the detection of reducing environments. Angew Chem Int Ed Engl. 54:1007–1010. 2015. View Article : Google Scholar
86	Chen S, Yang Y, Li H, Zhou X and Liu M: pH-Triggered Au-fluorescent mesoporous silica nanoparticles for 19F MR/fluorescent multimodal cancer cellular imaging. Chem Commun (Camb). 50:283–285. 2014. View Article : Google Scholar
87	Mizukami S, Takikawa R, Sugihara F, Shirakawa M and Kikuchi K: Dual-function probe to detect protease activity for fluorescence measurement and 19F MRI. Angew Chem Int Ed Engl. 48:3641–3643. 2009. View Article : Google Scholar : PubMed/NCBI
88	Fu C, Tang J, Pye A, Liu T, Zhang C, Tan X, Han F, Peng H and Whittaker AK: Fluorinated glycopolymers as reduction-responsive ¹⁹F MRI agents for targeted imaging of cancer. Biomacromolecules. 20:2043–2050. 2019. View Article : Google Scholar : PubMed/NCBI
89	Wang K, Peng H, Thurecht KJ, Puttick S and Whittaker AK: Segmented highly branched copolymers: Rationally designed macromolecules for improved and tunable (19)F MRI. Biomacromolecules. 16:2827–2839. 2015. View Article : Google Scholar : PubMed/NCBI
90	Alhaidari LM and Spain SG: Synthesis of 5-fluorouracil polymer conjugate and ¹⁹F NMR analysis of drug release for MRI monitoring. Polymers (Basel). 15:17782023. View Article : Google Scholar
91	Krawczyk T, Minoshima M, Sugihara F and Kikuchi K: Modified polysaccharides as potential (19)F magnetic resonance contrast agents. Carbohydr Res. 428:72–78. 2016. View Article : Google Scholar : PubMed/NCBI
92	Yang X, Sun Y, Kootala S, Hilborn J, Heerschap A and Ossipov D: Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging. Carbohydr Polym. 110:95–99. 2014. View Article : Google Scholar : PubMed/NCBI
93	Bermejo-Velasco D, Dou W, Heerschap A, Ossipov D and Hilborn J: Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging. Carbohydr Polym. 197:641–648. 2018. View Article : Google Scholar : PubMed/NCBI
94	Strasser P, Schinegger V, Friske J, Brüggemann O, Helbich TH, Teasdale I and Pashkunova-Martic I: Superfluorinated, highly water-soluble polyphosphazenes as potential ¹⁹F magnetic resonance imaging (MRI) contrast agents. J Funct Biomater. 15:402024. View Article : Google Scholar
95	Han J, Duan Z, Liu C, Liu Y, Zhao X, Wang B, Cao S and Wu D: Hyperbranched polymeric ¹⁹F MRI contrast agents with long T₂ relaxation time based on β-cyclodextrin and phosphorycholine. Biomacromolecules. 25:5860–5872. 2024. View Article : Google Scholar : PubMed/NCBI
96	Rolfe BE, Blakey I, Squires O, Peng H, Boase NR, Alexander C, Parsons PG, Boyle GM, Whittaker AK and Thurecht KJ: Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imaging in vivo. J Am Chem Soc. 136:2413–2419. 2014. View Article : Google Scholar : PubMed/NCBI
97	Feng Z, Li Q, Wang W, Ni Q, Wang Y, Song H, Zhang C, Kong D, Liang XJ and Huang P: Superhydrophilic fluorinated polymer and nanogel for high-performance ¹⁹F magnetic resonance imaging. Biomaterials. 256:1201842020. View Article : Google Scholar
98	Thurecht KJ, Blakey I, Peng H, Squires O, Hsu S, Alexander C and Whittaker AK: Functional hyperbranched polymers: Toward targeted in vivo 19F magnetic resonance imaging using designed macromolecules. J Am Chem Soc. 132:5336–5337. 2010. View Article : Google Scholar : PubMed/NCBI
99	Le Droumaguet B and Velonia K: Click chemistry: A powerful tool to create polymer-based macromolecular chimeras. Macromol Rapid Commun. 29:1073–1089. 2008. View Article : Google Scholar
100	Chen S, Xiao L, Li Y, Qiu M, Yuan Y, Zhou R, Li C, Zhang L, Jiang ZX, Liu M and Zhou X: In vivo nitroreductase imaging via fluorescence and chemical shift dependent ¹⁹F NMR. Angew Chem. 134:e2022134952022. View Article : Google Scholar
101	Xu SY, Guo C, Pan K and Wang L: Combined fluorescence and MRI in bioimaging. Imaging Tools for Chemical Biology. 157–179. 2024. View Article : Google Scholar
102	Fu Q, Yang X, Wang M, Zhu K, Wang Y and Song J: Activatable probes for ratiometric imaging of endogenous biomarkers in vivo. ACS Nano. 18:3916–3968. 2024. View Article : Google Scholar : PubMed/NCBI
103	Yang L, Hou H and Li J: Frontiers in fluorescence imaging: tools for the in situ sensing of disease biomarkers. J Mater Chem B. 13:1133–1158. 2025. View Article : Google Scholar
104	Akazawa K, Sugihara F, Nakamura T, Mizukami S and Kikuchi K: Highly sensitive detection of caspase-3/7 activity in living mice using enzyme-responsive ¹⁹F MRI nanoprobes. Bioconjug Chem. 29:1720–1728. 2018. View Article : Google Scholar : PubMed/NCBI
105	Shusterman-Krush R, Tirukoti ND, Bandela AK, Avram L, Allouche-Arnon H, Cai X, Gibb BC and Bar-Shir A: Single fluorinated agent for multiplexed ¹⁹F-MRI with micromolar detectability based on dynamic exchange. Angew Chem Int Ed Engl. 60:15405–15411. 2021. View Article : Google Scholar : PubMed/NCBI
106	Jones KM, Pollard AC and Pagel MD: Clinical applications of chemical exchange saturation transfer (CEST) MRI. J Magn Reson Imaging. 47:11–27. 2018. View Article : Google Scholar :
107	Banerjee SR, Song X, Yang X, Minn I, Lisok A, Chen Y, Bui A, Chatterjee S, Chen J, van Zijl PCM, et al: Salicylic acid-based polymeric contrast agents for molecular magnetic resonance imaging of prostate cancer. Chemistry. 24:7235–7242. 2018. View Article : Google Scholar : PubMed/NCBI
108	Janasik D and Krawczyk T: ¹⁹F MRI probes for multimodal imaging. Chemistry. 28:e2021025562022. View Article : Google Scholar
109	Chen H, Viel S, Ziarelli F and Peng L: 19F NMR: A valuable tool for studying biological events. Chem Soc Rev. 42:7971–7982. 2013. View Article : Google Scholar : PubMed/NCBI
110	Yang J, Li Y, Sun J, Zou H, Sun Y, Luo J, Xie Q, A R, Wang H, Li X, et al: An osimertinib-perfluorocarbon nanoemulsion with excellent targeted therapeutic efficacy in non-small cell lung cancer: Achieving intratracheal and intravenous administration. ACS Nano. 16:12590–12605. 2022. View Article : Google Scholar : PubMed/NCBI
111	Takaoka Y, Sakamoto T, Tsukiji S, Narazaki M, Matsuda T, Tochio H, Shirakawa M and Hamachi I: Self-assembling nanoprobes that display off/on 19F nuclear magnetic resonance signals for protein detection and imaging. Nat Chem. 1:557–561. 2009. View Article : Google Scholar : PubMed/NCBI
112	Akazawa K, Sugihara F, Nakamura T, Matsushita H, Mukai H, Akimoto R, Minoshima M, Mizukami S and Kikuchi K: Perfluorocarbon-based ¹⁹F MRI nanoprobes for in vivo multicolor imaging. Angew Chem. 130:16984–16989. 2018. View Article : Google Scholar
113	Akazawa K, Sugihara F, Minoshima M, Mizukami S and Kikuchi K: Sensing caspase-1 activity using activatable ¹⁹F MRI nanoprobes with improved turn-on kinetics. Chem Commun (Camb). 54:11785–11788. 2018. View Article : Google Scholar : PubMed/NCBI
114	Yue X, Wang Z, Zhu L, Wang Y, Qian C, Ma Y, Kiesewetter DO, Niu G and Chen X: Novel 19F activatable probe for the detection of matrix metalloprotease-2 activity by MRI/MRS. Mol Pharm. 11:4208–4217. 2014. View Article : Google Scholar : PubMed/NCBI
115	Guo C, Zhang Y, Li Y, Xu S and Wang L: ¹⁹F MRI nanoprobes for the turn-on detection of phospholipase A2 with a low background. Anal Chem. 91:8147–8153. 2019. View Article : Google Scholar : PubMed/NCBI
116	Szczęch M, Łopuszyńska N, Tomal W, Jasiński K, Węglarz WP, Warszyński P and Szczepanowicz K: Nafion-based nanocarriers for fluorine magnetic resonance imaging. Langmuir. 36:9534–9539. 2020. View Article : Google Scholar
117	Hill LK, Frezzo JA, Katyal P, Hoang DM, Ben Youss Gironda Z, Xu C, Xie X, Delgado-Fukushima E, Wadghiri YZ and Montclare JK: Protein-engineered nanoscale micelles for dynamic ¹⁹F magnetic resonance and therapeutic drug delivery. ACS Nano. 13:2969–2985. 2019. View Article : Google Scholar : PubMed/NCBI
118	Bouchoucha M, van Heeswijk RB, Gossuin Y, Kleitz F and Fortin MA: Fluorinated mesoporous silica nanoparticles for binuclear probes in ¹H and ¹⁹F magnetic resonance imaging. Langmuir. 33:10531–10542. 2017. View Article : Google Scholar : PubMed/NCBI
119	Chen H, Song M, Tang J, Hu G, Xu S, Guo Z, Li N, Cui J, Zhang X, Chen X and Wang L: Ultrahigh (19)F loaded Cu1.75S nanoprobes for simultaneous (19)F magnetic resonance imaging and photothermal therapy. ACS Nano. 10:1355–1362. 2016. View Article : Google Scholar : PubMed/NCBI
120	Kolouchova K, Sedlacek O, Jirak D, Babuka D, Blahut J, Kotek J, Vit M, Trousil J, Konefał R, Janouskova O, et al: Self-assembled thermoresponsive polymeric nanogels for ¹⁹F MR imaging. Biomacromolecules. 19:3515–3524. 2018. View Article : Google Scholar : PubMed/NCBI
121	Oishi M, Sumitani S and Nagasaki Y: On-off regulation of 19F magnetic resonance signals based on pH-sensitive PEGylated nanogels for potential tumor-specific smart 19F MRI probes. Bioconjug Chem. 18:1379–1382. 2007. View Article : Google Scholar : PubMed/NCBI
122	Munkhbat O, Canakci M, Zheng S, Hu W, Osborne B, Bogdanov AA and Thayumanavan S: ¹⁹F MRI of polymer nanogels aided by improved segmental mobility of embedded fluorine moieties. Biomacromolecules. 20:790–800. 2019. View Article : Google Scholar :
123	Peng H, Blakey I, Dargaville B, Rasoul F, Rose S and Whittaker AK: Synthesis and evaluation of partly fluorinated block copolymers as MRI imaging agents. Biomacromolecules. 10:374–381. 2009. View Article : Google Scholar : PubMed/NCBI
124	Barnett BP, Ruiz-Cabello J, Hota P, Ouwerkerk R, Shamblott MJ, Lauzon C, Walczak P, Gilson WD, Chacko VP, Kraitchman DL, et al: Use of perfluorocarbon nanoparticles for non-invasive multimodal cell tracking of human pancreatic islets. Contrast Media Mol Imaging. 6:251–259. 2011. View Article : Google Scholar : PubMed/NCBI
125	Xu X, Zhang R, Liu F, Ping J, Wen X, Wang H, Wang K, Sun X, Zou H, Shen B and Wu L: ¹⁹F MRI in orthotopic cancer model via intratracheal administration of α_νβ₃-targeted perfluorocarbon nanoparticles. Nanomedicine (Lond). 13:2551–2562. 2018. View Article : Google Scholar : PubMed/NCBI
126	Jirát-Ziółkowska N, Panakkal VM, Jiráková K, Havlíček D, Sedláček O and Jirák D: Cationic fluorinated micelles for cell labeling and ¹⁹F-MR imaging. Sci Rep. 14:226132024. View Article : Google Scholar
127	Matsushita H, Mizukami S, Sugihara F, Nakanishi Y, Yoshioka Y and Kikuchi K: Multifunctional core-shell silica nanoparticles for highly sensitive 19F magnetic resonance imaging. Angew Chem. 126:1026–1029. 2014. View Article : Google Scholar
128	Staal AHJ, Becker K, Tagit O, Koen van Riessen N, Koshkina O, Veltien A, Bouvain P, Cortenbach KRG, Scheenen T, Flögel U, et al: In vivo clearance of ¹⁹F MRI imaging nanocarriers is strongly influenced by nanoparticle ultrastructure. Biomaterials. 261:1203072020. View Article : Google Scholar
129	Cho MH, Shin SH, Park SH, Kadayakkara DK, Kim D and Choi Y: Targeted, stimuli-responsive, and theranostic ¹⁹F magnetic resonance imaging probes. Bioconjug Chem. 30:2502–2518. 2019. View Article : Google Scholar : PubMed/NCBI
130	Lyu Z, Ralahy B, Perles-Barbacaru TA, Ding L, Jiang Y, Lian B, Roussel T, Liu X, Galanakou C, Laurini E, et al: Self-assembling dendrimer nanosystems for specific fluorine magnetic resonance imaging and effective theranostic treatment of tumors. Proc Natl Acad Sci USA. 121:e23224031212024. View Article : Google Scholar : PubMed/NCBI
131	Criscione JM, Le BL, Stern E, Brennan M, Rahner C, Papademetris X and Fahmy TM: Self-assembly of pH-responsive fluorinated dendrimer-based particulates for drug delivery and noninvasive imaging. Biomaterials. 30:3946–3955. 2009. View Article : Google Scholar : PubMed/NCBI
132	Xu H, Kim D, Zhao YY, Kim C, Song G, Hu Q, Kang H and Yoon J: Remote control of energy transformation-based cancer imaging and therapy. Adv Mater. 36:e24028062024. View Article : Google Scholar : PubMed/NCBI
133	Svenson S: The dendrimer paradox-high medical expectations but poor clinical translation. Chem Soc Rev. 44:4131–4144. 2015. View Article : Google Scholar : PubMed/NCBI
134	Cooke DJ, Maier EY, King TL, Lin H, Hendrichs S, Lee S, Mafy NN, Scott KM, Lu Y and Que EL: Dual nanoparticle conjugates for highly sensitive and versatile sensing using ¹⁹F magnetic resonance imaging. Angew Chem Int Ed Engl. 63:e2023123222024. View Article : Google Scholar
135	Wang C, Adams SR and Ahrens ET: Emergent fluorous molecules and their uses in molecular imaging. Acc Chem Res. 54:3060–3070. 2021. View Article : Google Scholar : PubMed/NCBI
136	Bo S, Yuan Y, Chen Y, Yang Z, Chen S, Zhou X and Jiang ZX: In vivo drug tracking with ¹⁹F MRI at therapeutic dose. Chem Commun (Camb). 54:3875–3878. 2018. View Article : Google Scholar : PubMed/NCBI
137	Li L, Li A, Lin Y, Chen D, Kang B, Lin H and Gao J: An activatable ¹⁹F MRI molecular probe for sensing and imaging of norepinephrine. ChemistryOpen. 11:e2022001102022. View Article : Google Scholar
138	Koshkina O, White PB, Staal AHJ, Schweins R, Swider E, Tirotta I, Tinnemans P, Fokkink R, Veltien A, van Riessen NK, et al: Nanoparticles for 'two color' ¹⁹F magnetic resonance imaging: Towards combined imaging of biodistribution and degradation. J Colloid Interface Sci. 565:278–287. 2020. View Article : Google Scholar : PubMed/NCBI
139	Kadjane P, Platas-Iglesias C, Boehm-Sturm P, Truffault V, Hagberg G, Hoehn M, Logothetis N and Angelovski G: Dual-frequency calcium-responsive MRI agents. Chem Eur J. 20:7351–7362. 2014. View Article : Google Scholar : PubMed/NCBI
140	Doura T, Hata R, Nonaka H, Sugihara F, Yoshioka Y and Sando S: An adhesive (19)F MRI chemical probe allows signal off-to-on-type molecular sensing in a biological environment. Chem Commun (Camb). 49:11421–11423. 2013. View Article : Google Scholar : PubMed/NCBI
141	Southworth R, Parry CR, Parkes HG, Medina RA and Garlick PB: Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P: A 19F NMR spectroscopy study in the rat. NMR Biomed. 16:494–502. 2003. View Article : Google Scholar : PubMed/NCBI
142	Kanazawa Y, Umayahara K, Shimmura T and Yamashita T: 19F NMR of 2-deoxy-2-fluoro-D-glucose for tumor diagnosis in mice. An NDP-bound hexose analog as a new NMR target for imaging. NMR Biomed. 10:35–41. 1997. View Article : Google Scholar : PubMed/NCBI
143	Pujales-Paradela R, Savić T, Esteban-Gómez D, Angelovski G, Carniato F, Botta M and Platas-Iglesias C: Gadolinium(III)-based dual ¹H/¹⁹F magnetic resonance imaging probes. Chem Eur J. 25:4782–4792. 2019. View Article : Google Scholar
144	Yu JX, Kodibagkar VD, Cui W and Mason RP: 19F: A versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. Curr Med Chem. 12:819–848. 2005. View Article : Google Scholar : PubMed/NCBI
145	Bo S, Song C, Li Y, Yu W, Chen S, Zhou X, Yang Z, Zheng X and Jiang ZX: Design and synthesis of fluorinated amphiphile as (19)F MRI/fluorescence dual-imaging agent by tuning the self-assembly. J Org Chem. 80:6360–6366. 2015. View Article : Google Scholar : PubMed/NCBI
146	Chen D, Lin Y, Li A, Luo X, Yang C, Gao J and Lin H: Bio-orthogonal metabolic fluorine labeling enables deep-tissue visualization of tumor cells in vivo by ¹⁹F magnetic resonance imaging. Anal Chem. 94:16614–16621. 2022. View Article : Google Scholar : PubMed/NCBI
147	Cabanac S, Malet-Martino MC, Bon M, Martino R, Nedelec JF and Dimicoli JL: Direct 19f NMR spectroscopic observation of 5-fluorouracil metabolism in the isolated perfused mouse liver model. NMR Biomed. 1:113–120. 1988. View Article : Google Scholar : PubMed/NCBI
148	Wei H, Frey AM and Jasanoff A: Molecular fMRI of neurochemical signaling. J Neurosci Methods. 364:1093722021. View Article : Google Scholar : PubMed/NCBI
149	Matsuo K, Kamada R, Mizusawa K, Imai H, Takayama Y, Narazaki M, Matsuda T, Takaoka Y and Hamachi I: Specific detection and imaging of enzyme activity by signal-amplifiable self-assembling (19)F MRI probes. Chemistry. 19:12875–12883. 2013. View Article : Google Scholar : PubMed/NCBI
150	Wibowo A, Park JM, Liu SC, Khosla C and Spielman DM: Real-time in vivo detection of H₂O₂ using hyperpolarized ¹³C-thiourea. ACS Chem Biol. 12:1737–1742. 2017. View Article : Google Scholar : PubMed/NCBI
151	Doura T, Hata R, Nonaka H, Ichikawa K and Sando S: Design of a 13C magnetic resonance probe using a deuterated methoxy group as a long-lived hyperpolarization unit. Angew Chem Int Ed Engl. 51:10114–10117. 2012. View Article : Google Scholar : PubMed/NCBI
152	Nonaka H, Hata R, Doura T, Nishihara T, Kumagai K, Akakabe M, Tsuda M, Ichikawa K and Sando S: A platform for designing hyperpolarized magnetic resonance chemical probes. Nat Commun. 4:24112013. View Article : Google Scholar : PubMed/NCBI
153	Lippert AR, Keshari KR, Kurhanewicz J and Chang CJ: A hydrogen peroxide-responsive hyperpolarized 13C MRI contrast agent. J Am Chem Soc. 133:3776–3779. 2011. View Article : Google Scholar : PubMed/NCBI
154	Zhao J, Chen J, Ma S, Liu Q, Huang L, Chen X, Lou K and Wang W: Recent developments in multimodality fluorescence imaging probes. Acta Pharm Sin B. 8:320–338. 2018. View Article : Google Scholar : PubMed/NCBI
155	Vivian D, Cheng K, Khurana S, Xu S, Dawson PA, Raufman JP and Polli JE: Design and evaluation of a novel trifluorinated imaging agent for assessment of bile acid transport using fluorine magnetic resonance imaging. J Pharm Sci. 103:3782–3792. 2014. View Article : Google Scholar : PubMed/NCBI
156	Tanifum EA, Devkota L, Ngwa C, Badachhape AA, Ghaghada KB, Romero J, Pautler RG and Annapragada AV: A hyperfluorinated hydrophilic molecule for aqueous ¹⁹F MRI contrast media. Contrast Media Mol Imaging. 2018:16935132018. View Article : Google Scholar
157	Du L, Helsper S, Nosratabad NA, Wang W, Fadool DA, Amiens C, Grant S and Mattoussi H: A multifunctional contrast agent for ¹⁹F-based magnetic resonance imaging. Bioconjug Chem. 33:881–891. 2022. View Article : Google Scholar : PubMed/NCBI
158	Pavlova OS, Anisimov NV, Gervits LL, Gulyaev MV, Semenova VN, Pirogov YA and Panchenko VY: ¹⁹ F MRI of human lungs at 0.5 Tesla using octafluorocyclobutane. Magn Reson Med. 84:2117–2123. 2020. View Article : Google Scholar : PubMed/NCBI
159	Li Q, Feng Z, Song H, Zhang J, Dong A, Kong D, Wang W and Huang P: ¹⁹F magnetic resonance imaging enabled real-time, non-invasive and precise localization and quantification of the degradation rate of hydrogel scaffolds in vivo. Biomater Sci. 8:3301–3309. 2020. View Article : Google Scholar : PubMed/NCBI
160	Liang S, Louchami K, Kolster H, Jacobsen A, Zhang Y, Thimm J, Sener A, Thiem J, Malaisse W, Dresselaers T and Himmelreich U: In vivo and ex vivo 19-fluorine magnetic resonance imaging and spectroscopy of beta-cells and pancreatic islets using GLUT-2 specific contrast agents. Contrast Media Mol Imaging. 11:506–513. 2016. View Article : Google Scholar : PubMed/NCBI
161	Wu B, Warnock G, Zaiss M, Lin C, Chen M, Zhou Z, Mu L, Nanz D, Tuura R and Delso G: An overview of CEST MRI for non-MR physicists. EJNMMI Phys. 3:192016. View Article : Google Scholar : PubMed/NCBI
162	Goldenberg JM and Pagel MD: Assessments of tumor metabolism with CEST MRI. NMR Biomed. 32:e39432019. View Article : Google Scholar
163	Wolff SD and Balaban RS: Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med. 10:135–144. 1989. View Article : Google Scholar : PubMed/NCBI
164	Pavuluri K, Manoli I, Pass A, Li Y, Vernon HJ, Venditti CP and McMahon MT: Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging. Sci Adv. 5:eaaw83572019. View Article : Google Scholar : PubMed/NCBI
165	Rivlin M and Navon G: Glucosamine and N-acetyl glucosamine as new CEST MRI agents for molecular imaging of tumors. Sci Rep. 6:326482016. View Article : Google Scholar : PubMed/NCBI
166	Nasrallah FA, Pagès G, Kuchel PW, Golay X and Chuang KH: Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI. J Cereb Blood Flow Metab. 33:1270–1278. 2013. View Article : Google Scholar : PubMed/NCBI
167	Zhou J, Lal B, Wilson DA, Laterra J and Van Zijl PCM: Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med. 50:1120–1126. 2003. View Article : Google Scholar : PubMed/NCBI
168	Ngen EJ, Bar-Shir A, Jablonska A, Liu G, Song X, Ansari R, Bulte JW, Janowski M, Pearl M, Walczak P and Gilad AA: Imaging the DNA alkylator melphalan by CEST MRI: An advanced approach to theranostics. Mol Pharm. 13:3043–3053. 2016. View Article : Google Scholar : PubMed/NCBI
169	Cai K, Xu HN, Singh A, Moon L, Haris M, Reddy R and Li LZ: Breast cancer redox heterogeneity detectable with chemical exchange saturation transfer (CEST) MRI. Mol Imaging Biol. 16:670–679. 2014. View Article : Google Scholar : PubMed/NCBI
170	Rivlin M, Horev J, Tsarfaty I and Navon G: Molecular imaging of tumors and metastases using chemical exchange saturation transfer (CEST) MRI. Sci Rep. 3:30452013. View Article : Google Scholar : PubMed/NCBI
171	Gao T, Zou C, Li Y, Jiang Z, Tang X and Song X: A brief history and future prospects of CEST MRI in clinical non-brain tumor imaging. Int J Mol Sci. 22:115592021. View Article : Google Scholar : PubMed/NCBI
172	Tang Y, Xiao G, Shen Z, Zhuang C, Xie Y, Zhang X, Yang Z, Guan J, Shen Y, Chen Y, et al: Noninvasive detection of extracellular pH in human benign and malignant liver tumors using CEST MRI. Front Oncol. 10:5789852020. View Article : Google Scholar : PubMed/NCBI
173	Kraiger M, Klein-Rodewald T, Rathkolb B, Calzada-Wack J, Sanz-Moreno A, Fuchs H, Wolf E, Gailus-Durner V and de Angelis MH: Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI. Sci Rep. 12:146082022. View Article : Google Scholar : PubMed/NCBI
174	Barenholz Y: Doxil^®-the first FDA-approved nano-drug: Lessons learned. J Control Release. 160:117–134. 2012. View Article : Google Scholar : PubMed/NCBI
175	Chan KW, McMahon MT, Kato Y, Liu G, Bulte JW, Bhujwalla ZM, Artemov D and van Zijl PC: Natural D-glucose as a biodegradable MRI contrast agent for detecting cancer. Magn Reson Med. 68:1764–1773. 2012. View Article : Google Scholar : PubMed/NCBI
176	Xu X, Sehgal AA, Yadav NN, Laterra J, Blair L, Blakeley J, Seidemo A, Coughlin JM, Pomper MG, Knutsson L and van Zijl PCM: d-glucose weighted chemical exchange saturation transfer (glucoCEST)-based dynamic glucose enhanced (DGE) MRI at 3T: Early experience in healthy volunteers and brain tumor patients. Magn Reson Med. 84:247–262. 2020. View Article : Google Scholar
177	Durmo F, Rydhög A, Testud F, Lätt J, Schmitt B, Rydelius A, Englund E, Bengzon J, van Zijl P, Knutsson L and Sundgren PC: Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas. PLoS One. 15:e02440032020. View Article : Google Scholar : PubMed/NCBI
178	Paech D, Windschuh J, Oberhollenzer J, Dreher C, Sahm F, Meissner JE, Goerke S, Schuenke P, Zaiss M, Regnery S, et al: Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T. Neuro Oncol. 20:1661–1671. 2018. View Article : Google Scholar : PubMed/NCBI
179	Schmitt B, Zamecnik P, Zaiss M, Rerich E, Schuster L, Bachert P and Schlemmer HP: A new contrast in MR mammography by means of chemical exchange saturation transfer (CEST) imaging at 3 Tesla: Preliminary results. Rofo. 183:1030–1036. 2011. View Article : Google Scholar : PubMed/NCBI
180	Zhou Y, van Zijl PCM, Xu X, Li Y, Chen L and Yadav NN: Magnetic resonance imaging of glycogen using its magnetic coupling with water. Proc Natl Acad Sci USA. 117:3144–3149. 2020. View Article : Google Scholar : PubMed/NCBI
181	Yuwen Zhou I, Wang E, Cheung JS, Lu D, Ji Y, Zhang X, Fulci G and Sun PZ: Direct saturation-corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear Overhauser effect contrasts. Magn Reson Med. 78:2307–2314. 2017. View Article : Google Scholar : PubMed/NCBI
182	Zhou J, Payen JF and Van Zijl PC: The interaction between magnetization transfer and blood-oxygen-level-dependent effects. Magn Reson Med. 53:356–366. 2005. View Article : Google Scholar : PubMed/NCBI
183	Seidemo A, Lehmann PM, Rydhög A, Wirestam R, Helms G, Zhang Y, Yadav NN, Sundgren PC, van Zijl PCM and Knutsson L: Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time. NMR Biomed. 35:e46242022. View Article : Google Scholar
184	Xu X, Yadav NN, Knutsson L, Hua J, Kalyani R, Hall E, Laterra J, Blakeley J, Strowd R, Pomper M, et al: Dynamic glucose-enhanced (DGE) MRI: Translation to human scanning and first results in glioma patients. Tomography. 1:105–114. 2015. View Article : Google Scholar
185	Knutsson L, Xu X, van Zijl PCM and Chan KWY: Imaging of sugar-based contrast agents using their hydroxyl proton exchange properties. NMR Biomed. 36:e47842023. View Article : Google Scholar
186	Kim M, Torrealdea F, Adeleke S, Rega M, Evans V, Beeston T, Soteriou K, Thust S, Kujawa A, Okuchi S, et al: Challenges in glucoCEST MR body imaging at 3 Tesla. Quant Imaging Med Surg. 9:16282019. View Article : Google Scholar : PubMed/NCBI
187	Sehgal AA, Li Y, Lal B, Yadav NN, Xu X, Xu J, Laterra J and van Zijl PCM: CEST MRI of 3-O-methyl-D-glucose uptake and accumulation in brain tumors. Magn Reson Med. 81:1993–2000. 2019. View Article : Google Scholar :
188	Ling W, Regatte RR, Navon G and Jerschow A: Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc Natl Acad Sci USA. 105:2266–2270. 2008. View Article : Google Scholar : PubMed/NCBI
189	Rivlin M and Navon G: Phosphate buffer-catalyzed kinetics of mutarotation of glucosamine investigated by NMR spectroscopy. Carbohydr Res. 517:1085812022. View Article : Google Scholar : PubMed/NCBI
190	Bagga P, Wilson N, Rich L, Marincola FM, Schnall MD, Hariharan H, Haris M and Reddy R: Sugar alcohol provides imaging contrast in cancer detection. Sci Rep. 9:110922019. View Article : Google Scholar : PubMed/NCBI
191	Wang J, Fukuda M, Chung JJ, Wang P and Jin T: Chemical exchange sensitive MRI of glucose uptake using xylose as a contrast agent. Magn Reson Med. 85:1953–1961. 2021. View Article : Google Scholar :
192	Han Z, Chen C, Xu X, Bai R, Staedtke V, Huang J, Chan KWY, Xu J, Kamson DO, Wen Z, et al: Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran. NMR Biomed. 35:e46492022. View Article : Google Scholar :
193	Huang J, Chen Z, Park SW, Lai JHC and Chan KWY: Molecular imaging of brain tumors and drug delivery using CEST MRI: Promises and challenges. Pharmaceutics. 14:4512022. View Article : Google Scholar : PubMed/NCBI
194	Pavuluri K, Rosenberg JT, Helsper S, Bo S and McMahon MT: Amplified detection of phosphocreatine and creatine after supplementation using CEST MRI at high and ultrahigh magnetic fields. J Magn Reson. 313:1067032020. View Article : Google Scholar : PubMed/NCBI
195	Liu J, Xie CM, Liu Q, Xu J, Zheng LY, Liu X, Zheng H and Wu Y: Dynamic alteration in myocardium creatine during acute infarction using MR CEST imaging. NMR Biomed. 35:e47042022. View Article : Google Scholar : PubMed/NCBI
196	Ohno K, Ohkubo M, Zheng B, Watanabe M, Matsuda T, Kwee IL and Igarashi H: GlyCEST: Magnetic resonance imaging of glycine-distribution in the normal murine brain and alterations in 5xFAD mice. Contrast Media Mol Imaging. 2021:89887622021. View Article : Google Scholar
197	Jin T, Wang P, Zong X and Kim SG: Magnetic resonance imaging of the amine-proton exchange (APEX) dependent contrast. Neuroimage. 59:1218–1227. 2012. View Article : Google Scholar
198	Zhang J, Yuan Y, Han Z, Li Y, van Zijl PCM, Yang X, Bulte JWM and Liu G: Detecting acid phosphatase enzymatic activity with phenol as a chemical exchange saturation transfer magnetic resonance imaging contrast agent (PhenolCEST MRI). Biosens Bioelectron. 141:1114422019. View Article : Google Scholar : PubMed/NCBI
199	Huang J, Lai JHC, Tse KH, Cheng GWY, Liu Y, Chen Z, Han X, Chen L, Xu J and Chan KWY: Deep neural network based CEST and AREX processing: Application in imaging a model of Alzheimer's disease at 3 T. Magn Reson Med. 87:1529–1545. 2022. View Article : Google Scholar
200	Shin SH, Wendland MF, Zhang B, Tran A, Tang A and Vandsburger MH: Noninvasive imaging of renal urea handling by CEST-MRI. Magn Reson Med. 83:1034–1044. 2020. View Article : Google Scholar
201	Shin SH, Wendland MF and Vandsburger MH: Delayed urea differential enhancement CEST (dudeCEST)-MRI with T₁ correction for monitoring renal urea handling. Magn Reson Med. 85:2791–2804. 2021. View Article : Google Scholar
202	Stabinska J, Keupp J and McMahon MT: CEST MRI for monitoring kidney diseases. Advanced Clinical MRI of the Kidney: Methods and Protocols. Springer International Publishing; pp. 345–360. 2023, View Article : Google Scholar
203	Yang X, Song X, Ray Banerjee S, Li Y, Byun Y, Liu G, Bhujwalla ZM, Pomper MG and McMahon MT: Developing imidazoles as CEST MRI pH sensors. Contrast Media Mol Imaging. 11:304–312. 2016. View Article : Google Scholar : PubMed/NCBI
204	Longo DL, Sun PZ, Consolino L, Michelotti FC, Uggeri F and Aime S: A general MRI-CEST ratiometric approach for pH imaging: Demonstration of in vivo pH mapping with iobitridol. J Am Chem Soc. 136:14333–14336. 2014. View Article : Google Scholar : PubMed/NCBI
205	Sherry AD and Woods M: Chemical exchange saturation transfer contrast agents for magnetic resonance imaging. Annu Rev Biomed Eng. 10:391–411. 2008. View Article : Google Scholar : PubMed/NCBI
206	Song X, Walczak P, He X, Yang X, Pearl M, Bulte JWM, Pomper MG, McMahon MT and Janowski M: Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion. J Cereb Blood Flow Metab. 36:1186–1194. 2016. View Article : Google Scholar : PubMed/NCBI
207	Yang X, Song X, Li Y, Liu G, Banerjee SR, Pomper MG and McMahon MT: Salicylic acid and analogues as diaCEST MRI contrast agents with highly shifted exchangeable proton frequencies. Angew Chem Int Ed Engl. 52:8116–8119. 2013. View Article : Google Scholar : PubMed/NCBI
208	Bar-Shir A, Liu G, Liang Y, Yadav NN, McMahon MT, Walczak P, Nimmagadda S, Pomper MG, Tallman KA, Greenberg MM, et al: Transforming thymidine into a magnetic resonance imaging probe for monitoring gene expression. J Am Chem Soc. 135:1617–1624. 2013. View Article : Google Scholar : PubMed/NCBI
209	Bo S, Stabinska J, Wu Y, Pavuluri KD, Singh A, Mohanta Z, Choudhry R, Kates M, Sedaghat F, Bhujwalla Z, et al: Exploring the potential of the novel imidazole-4,5-dicarboxyamide chemical exchange saturation transfer scaffold for pH and perfusion imaging. NMR Biomed. 36:e48942023. View Article : Google Scholar :
210	Longo DL, Carella A, Corrado A, Pirotta E, Mohanta Z, Singh A, Stabinska J, Liu G and McMahon MT: A snapshot of the vast array of diamagnetic CEST MRI contrast agents. NMR Biomed. 36:e47152023. View Article : Google Scholar
211	Bo S, Sedaghat F, Pavuluri K, Rowe SP, Cohen A, Kates M and McMahon MT: Dynamic contrast enhanced-MR CEST urography: An emerging tool in the diagnosis and management of upper urinary tract obstruction. Tomography. 7:80–94. 2021. View Article : Google Scholar : PubMed/NCBI
212	Pavuluri K, Yang E, Ayyappan V, Sonkar K, Tan Z, Tressler CM, Bo S, Bibic A, Glunde K and McMahon MT: Unlabeled aspirin as an activatable theranostic MRI agent for breast cancer. Theranostics. 12:1937–1951. 2022. View Article : Google Scholar : PubMed/NCBI
213	Song X, Yang X, Ray Banerjee S, Pomper MG and McMahon MT: Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. Contrast Media Mol Imaging. 10:74–80. 2015. View Article : Google Scholar
214	Yang X, Yadav NN, Song X, Ray Banerjee S, Edelman H, Minn I, van Zijl PC, Pomper MG and McMahon MT: Tuning phenols with intra-molecular bond shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents. Chemistry. 20:15824–15832. 2014. View Article : Google Scholar : PubMed/NCBI
215	Sinharay S, Randtke EA, Howison CM, Ignatenko NA and Pagel MD: Detection of enzyme activity and inhibition during studies in solution, in vitro and in vivo with catalyCEST MRI. Mol Imaging Biol. 20:240–248. 2018. View Article : Google Scholar :
216	Kombala CJ, Lokugama SD, Kotrotsou A, Li T, Pollard AC and Pagel MD: Simultaneous evaluations of pH and enzyme activity with a CEST MRI contrast agent. ACS Sens. 6:4535–4544. 2021. View Article : Google Scholar : PubMed/NCBI
217	Sinharay S, Randtke EA, Jones KM, Howison CM, Chambers SK, Kobayashi H and Pagel MD: Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI. Magn Reson Med. 77:2005–2014. 2017. View Article : Google Scholar
218	Hingorani DV, Montano LA, Randtke EA, Lee YS, Cárdenas-Rodríguez J and Pagel MD: A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. Contrast Media Mol Imaging. 11:130–138. 2016. View Article : Google Scholar
219	Longo DL, Michelotti F, Consolino L, Bardini P, Digilio G, Xiao G, Sun PZ and Aime S: In vitro and in vivo assessment of nonionic iodinated radiographic molecules as chemical exchange saturation transfer magnetic resonance imaging tumor perfusion agents. Invest Radiol. 51:155–162. 2016. View Article : Google Scholar
220	Liu J, Chu C, Zhang J, Bie C, Chen L, Aafreen S, Xu J, Kamson DO, van Zijl PCM, Walczak P, et al: Label-free assessment of mannitol accumulation following osmotic blood-brain barrier opening using chemical exchange saturation transfer magnetic resonance imaging. Pharmaceutics. 14:25292022. View Article : Google Scholar : PubMed/NCBI
221	Zhang X, Yuan Y, Li S, Zeng Q, Guo Q, Liu N, Yang M, Yang Y, Liu M, McMahon MT and Zhou X: Free-base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons. Magn Reson Med. 82:577–585. 2019. View Article : Google Scholar : PubMed/NCBI
222	Liu H, Jablonska A, Li Y, Cao S, Liu D, Chen H, Van Zijl PC, Bulte JW, Janowski M, Walczak P and Liu G: Label-free CEST MRI detection of citicoline-liposome drug delivery in ischemic stroke. Theranostics. 6:1588–1600. 2016. View Article : Google Scholar : PubMed/NCBI
223	Aime S, Calabi L, Biondi L, De Miranda M, Ghelli S, Paleari L, Rebaudengo C and Terreno E: Iopamidol: Exploring the potential use of a well-established x-ray contrast agent for MRI. Magn Reson Med. 53:830–834. 2005. View Article : Google Scholar : PubMed/NCBI
224	Li J, Feng X, Zhu W, Oskolkov N, Zhou T, Kim BK, Baig N, McMahon MT and Oldfield E: Chemical exchange saturation transfer (CEST) agents: Quantum chemistry and MRI. Chemistry. 22:264–271. 2016. View Article : Google Scholar :
225	Zhang H, Zhou J and Peng Y: Amide proton transfer-weighted MR imaging of pediatric central nervous system diseases. Magn Reson Imaging Clin N Am. 29:631–641. 2021. View Article : Google Scholar : PubMed/NCBI
226	Fillion AJ, Bricco AR, Lee HD, Korenchan DE, Farrar CT and Gilad AA: Development of a synthetic biosensor for chemical exchange MRI utilizing in silico optimized peptides. NMR Biomed. 36:e50072023. View Article : Google Scholar : PubMed/NCBI
227	Rosa E, Di Gregorio E, Ferrauto G, Diaferia C, Gallo E, Terreno E and Accardo A: Hybrid PNA-peptide hydrogels as injectable CEST-MRI agents. J Mater Chem B. 12:6371–6383. 2024. View Article : Google Scholar : PubMed/NCBI
228	Sartoretti E, Sartoretti T, Wyss M, Reischauer C, van Smoorenburg L, Binkert CA, Sartoretti-Schefer S and Mannil M: Amide proton transfer weighted (APTw) imaging based radiomics allows for the differentiation of gliomas from metastases. Sci Rep. 11:55062021. View Article : Google Scholar : PubMed/NCBI
229	Liang Y, Bar-Shir A, Song X, Gilad AA, Walczak P and Bulte JW: Label-free imaging of gelatin-containing hydrogel scaffolds. Biomaterials. 42:144–150. 2015. View Article : Google Scholar
230	Wu Y, Evbuomwan M, Melendez M, Opina A and Sherry AD: Advantages of macromolecular to nanosized chemical-exchange saturation transfer agents for MRI applications. Future Med Chem. 2:351–366. 2010. View Article : Google Scholar
231	Choi J, Kim K, Kim T, Liu G, Bar-Shir A, Hyeon T, McMahon MT, Bulte JW, Fisher JP and Gilad AA: Multimodal imaging of sustained drug release from 3-D poly(propylene fumarate) (PPF) scaffolds. J Control Release. 156:239–245. 2011. View Article : Google Scholar : PubMed/NCBI
232	McMahon MT, Gilad AA, DeLiso MA, Cromer Berman SM, Bulte JWM and Van Zijl PCM: New 'multicolor' polypeptide diamagnetic chemical exchange saturation transfer (DIACEST) contrast agents for MRI. Magn Reson Med. 60:803–812. 2008. View Article : Google Scholar : PubMed/NCBI
233	Zhou J, Payen JF, Wilson DA, Traystman RJ and Van Zijl PCM: Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med. 9:1085–1090. 2003. View Article : Google Scholar : PubMed/NCBI
234	McMahon MT, Gilad AA, Zhou J, Sun PZ, Bulte JWM and Van Zijl PCM: Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): pH calibration for poly-L-lysine and a starburst dendrimer. Magn Reson Med. 55:836–847. 2006. View Article : Google Scholar : PubMed/NCBI
235	Bar-Shir A, Liu G, Chan KWY, Oskolkov N, Song X, Yadav NN, Walczak P, McMahon MT, van Zijl PCM, Bulte JWM and Gilad AA: Human protamine-1 as an MRI reporter gene based on chemical exchange. ACS Chem Biol. 9:134–138. 2014. View Article : Google Scholar :
236	Bar-Shir A, Liang Y, Chan KWY, Gilad AA and Bulte JWM: Supercharged green fluorescent proteins as bimodal reporter genes for CEST MRI and optical imaging. Chem Commun (Camb). 51:4869–4871. 2015. View Article : Google Scholar : PubMed/NCBI
237	Oskolkov N, Bar-Shir A, Chan KWY, Song X, van Zijl PCM, Bulte JWM, Gilad AA and McMahon MT: Biophysical characterization of human protamine-1 as a responsive CEST MR contrast agent. ACS Macro Lett. 4:34–38. 2015. View Article : Google Scholar : PubMed/NCBI
238	Haris M, Singh A, Mohammed I, Ittyerah R, Nath K, Nanga RP, Debrosse C, Kogan F, Cai K, Poptani H, et al: In vivo magnetic resonance imaging of tumor protease activity. Sci Rep. 4:60812014. View Article : Google Scholar : PubMed/NCBI
239	Wang C, Lin G, Shen Z and Wang R: Angiopep-2 as an exogenous chemical exchange saturation transfer contrast agent in diagnosis of Alzheimer's disease. J Healthc Eng. 2022:74805192022.PubMed/NCBI
240	Sinharay S, Howison CM, Baker AF and Pagel MD: Detecting in vivo urokinase plasminogen activator activity with a catalyCEST MRI contrast agent. NMR Biomed. Mar 29–2017.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
241	Yuan Y, Raj P, Zhang J, Siddhanta S, Barman I and Bulte JWM: Furin-mediated self-assembly of olsalazine nanoparticles for targeted Raman imaging of tumors. Angew Chem. 133:3969–3973. 2021. View Article : Google Scholar
242	Kombala CJ, Kotrotsou A, Schuler FW, de la Cerda J, Ma JC, Zhang S and Pagel MD: Development of a nanoscale chemical exchange saturation transfer magnetic resonance imaging contrast agent that measures pH. ACS Nano. 15:20678–20688. 2021. View Article : Google Scholar : PubMed/NCBI
243	Goffeney N, Bulte JW, Duyn J, Bryant LH Jr and Van Zijl PC: Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange. J Am Chem Soc. 123:8628–8629. 2001. View Article : Google Scholar : PubMed/NCBI
244	Langereis S, Keupp J, van Velthoven JLJ, de Roos IHC, Burdinski D, Pikkemaat JA and Grüll H: A temperature-sensitive liposomal 1H CEST and 19F contrast agent for MR image-guided drug delivery. J Am Chem Soc. 131:1380–1381. 2009. View Article : Google Scholar : PubMed/NCBI
245	Zhang J, Yuan Y, Gao M, Han Z, Chu C, Li Y, van Zijl PCM, Ying M, Bulte JWM and Liu G: Carbon dots as a new class of diamagnetic chemical exchange saturation transfer (diaCEST) MRI contrast agents. Angew Chem Int Ed Engl. 58:9871–9875. 2019. View Article : Google Scholar : PubMed/NCBI
246	Chan KWY, Liu G, Song X, Kim H, Yu T, Arifin DR, Gilad AA, Hanes J, Walczak P, van Zijl PCM, et al: MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Nat Mater. 12:268–275. 2013. View Article : Google Scholar : PubMed/NCBI
247	Tyler B, Fowers KD, Li KW, Recinos VR, Caplan JM, Hdeib A, Grossman R, Basaldella L, Bekelis K, Pradilla G, et al: A thermal gel depot for local delivery of paclitaxel to treat experimental brain tumors in rats. J Neurosurg. 113:210–217. 2010. View Article : Google Scholar
248	Lesniak WG, Oskolkov N, Song X, Lal B, Yang X, Pomper M, Laterra J, Nimmagadda S and McMahon MT: Salicylic acid conjugated dendrimers are a tunable, high performance CEST MRI nanoplatform. Nano Lett. 16:2248–2253. 2016. View Article : Google Scholar : PubMed/NCBI
249	Pikkemaat J, Wegh R, Lamerichs R, van de Molengraaf RA, Langereis S, Burdinski D, Raymond AY, Janssen HM, de Waal BF, Willard NP, et al: Dendritic PARACEST contrast agents for magnetic resonance imaging. CContrast Media Mol Imaging. 2:229–239. 2007. View Article : Google Scholar
250	Ding L, Xu F, Luo B, Cheng L, Huang L, Jia Y and Ding J: Preparation of hematoporphyrin-poly(lactic acid) nanoparticles encapsulated perfluoropentane/salicylic acid for enhanced US/CEST MR bimodal imaging. Int J Nanomedicine. 19:4589–4605. 2024. View Article : Google Scholar : PubMed/NCBI
251	Yu T, Chan KWY, Anonuevo A, Song X, Schuster BS, Chattopadhyay S, Xu Q, Oskolkov N, Patel H, Ensign LM, et al: Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: Demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI). Nanomedicine. 11:401–405. 2015. View Article : Google Scholar
252	Lock LL, Li Y, Mao X, Chen H, Staedtke V, Bai R, Ma W, Lin R, Li Y, Liu G and Cui H: One-component supramolecular filament hydrogels as theranostic label-free magnetic resonance imaging agents. ACS Nano. 11:797–805. 2017. View Article : Google Scholar : PubMed/NCBI
253	Chakraborty S, Peruncheralathan S and Ghosh A: Paracetamol and other acetanilide analogs as inter-molecular hydrogen bonding assisted diamagnetic CEST MRI contrast agents. RSC Adv. 11:6526–6534. 2021. View Article : Google Scholar : PubMed/NCBI
254	Dang T, Suchy M, Truong YJ, Oakden W, Lam WW, Lazurko C, Facey G, Stanisz GJ and Shuhendler AJ: Hydrazo-CEST: hydrazone-dependent chemical exchange saturation transfer magnetic resonance imaging contrast agents. Chemistry. 24:9148–9156. 2018. View Article : Google Scholar : PubMed/NCBI
255	Cai X, Zhang J, Lu J, Yi L, Han Z, Zhang S, Yang X and Liu G: N-Aryl amides as chemical exchange saturation transfer magnetic resonance imaging contrast agents. Chemistry. 26:11705–11709. 2020. View Article : Google Scholar : PubMed/NCBI
256	Barandov A, Ghosh S and Jasanoff A: Probing nitric oxide signaling using molecular MRI. Free Radic Biol Med. 191:241–248. 2022. View Article : Google Scholar : PubMed/NCBI
257	Barandov A, Ghosh S, Li N, Bartelle BB, Daher JI, Pegis ML, Collins H and Jasanoff A: Molecular magnetic resonance imaging of nitric oxide in biological systems. ACS Sens. 5:1674–1682. 2020. View Article : Google Scholar : PubMed/NCBI
258	Xue X, Bo R, Qu H, Jia B, Xiao W, Yuan Y, Vapniarsky N, Lindstrom A, Wu H, Zhang D, et al: A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors. Biomaterials. 257:1202342020. View Article : Google Scholar : PubMed/NCBI
259	Brun EMSPT, Calvert ND, Suchý M, Kirby A, Melkus G, Garipov R, Addison CL and Shuhendler AJ: Mapping vitamin B₆ metabolism by hydrazoCEST magnetic resonance imaging. Chem Commun (Camb). 57:10867–10870. 2021. View Article : Google Scholar : PubMed/NCBI
260	Hosain MZ, Hyodo F, Mori T, Takahashi K, Nagao Y, Eto H, Murata M, Akahoshi T, Matsuo M and Katayama Y: Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism. Sci Rep. 10:164892020. View Article : Google Scholar : PubMed/NCBI
261	Matsumoto KI, Nakanishi I, Zhelev Z, Bakalova R and Aoki I: Nitroxyl radical as a theranostic contrast agent in magnetic resonance redox imaging. Antioxid Redox Signal. 36:95–121. 2022. View Article : Google Scholar :
262	Adachi K, Hyodo F, Elhelaly A, Mori T, Taniguchi T, Nakaya S and Matsuo M: Spatiotemporal evaluation of the early inflammatory response of the gut to radiation using non-invasive in vivo redox imaging. Int J Radiat Oncol Biol Phys. 120:e346–e347. 2024. View Article : Google Scholar
263	Koyasu N, Hyodo F, Iwasaki R, Eto H, Elhelaly AE, Tomita H, Shoda S, Takasu M, Mori T, Murata M, et al: Spatiotemporal imaging of redox status using in vivo dynamic nuclear polarization magnetic resonance imaging system for early monitoring of response to radiation treatment of tumor. Free Radic Biol Med. 179:170–180. 2022. View Article : Google Scholar
264	Yoshino Y, Fujii Y, Chihara K, Nakae A, Enmi JI, Yoshioka Y and Miyawaki I: Non-invasive differentiation of hepatic steatosis and steatohepatitis in a mouse model using nitroxyl radical as an MRI-contrast agent. Toxicol Rep. 12:1–9. 2023.
265	Matsumoto KI, Hyodo F, Matsumoto A, Koretsky AP, Sowers AL, Mitchell JB and Krishna MC: High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents. Clin Cancer Res. 12:2455–2462. 2006. View Article : Google Scholar : PubMed/NCBI
266	Shah SA, Cui SX, Waters CD, Sano S, Wang Y, Doviak H, Leor J, Walsh K, French BA and Epstein FH: Nitroxide-enhanced MRI of cardiovascular oxidative stress. NMR Biomed. 33:e43592020. View Article : Google Scholar : PubMed/NCBI
267	Kawano T, Murata M, Hyodo F, Eto H, Kosem N, Nakata R, Hamano N, Piao JS, Narahara S, Akahoshi T and Hashizume M: Noninvasive mapping of the redox status of dimethylnitrosamine-induced hepatic fibrosis using in vivo dynamic nuclear polarization-magnetic resonance imaging. Sci Rep. 6:326042016. View Article : Google Scholar : PubMed/NCBI
268	Kuroda Y, Togashi H, Uchida T, Haga K, Yamashita A and Sadahiro M: Oxidative stress evaluation of skeletal muscle in ischemia-reperfusion injury using enhanced magnetic resonance imaging. Sci Rep. 10:108632020. View Article : Google Scholar : PubMed/NCBI
269	Hyodo F, Eto H, Naganuma T, Koyasu N, Elhelaly AE, Noda Y, Kato H, Murata M, Akahoshi T, Hashizume M, et al: In vivo dynamic nuclear polarization magnetic resonance imaging for the evaluation of redox-related diseases and theranostics. Antioxid Redox Signal. 36:172–184. 2022. View Article : Google Scholar
270	Eto H, Murata M, Kawano T, Tachibana Y, Elhelaly AE, Noda Y, Kato H, Matsuo M and Hyodo F: Evaluation of the redox alteration in Duchenne muscular dystrophy model mice using in vivo DNP-MRI. Npj Imaging. 2:522024. View Article : Google Scholar
271	Tao Q, Zhang D, Zhang Q, Liu C, Ye S, Feng Y and Liu R: Mitochondrial targeted ROS scavenger based on nitroxide for treatment and MRI imaging of acute kidney injury. Free Radic Res. 56:303–315. 2022. View Article : Google Scholar : PubMed/NCBI
272	Eto H, Hyodo F, Kosem N, Kobayashi R, Yasukawa K, Nakao M, Kiniwa M and Utsumi H: Redox imaging of skeletal muscle using in vivo DNP-MRI and its application to an animal model of local inflammation. Free Radic Biol Med. 89:1097–1104. 2015. View Article : Google Scholar : PubMed/NCBI
273	Matsumoto KI, Yamasaki T, Nakamura M, Ishikawa J, Ueno M, Nakanishi I, Sekita A, Ozawa Y, Kamada T, Aoki I and Yamada K: Brain contrasting ability of blood-brain-barrier-permeable nitroxyl contrast agents for magnetic resonance redox imaging. Magn Reson Med. 76:935–945. 2016. View Article : Google Scholar
274	Hyodo F, Chuang KH, Goloshevsky AG, Sulima A, Griffiths GL, Mitchell JB, Koretsky AP and Krishna MC: Brain redox imaging using blood-brain barrier-permeable nitroxide MRI contrast agent. J Cereb Blood Flow Metab. 28:1165–1174. 2008. View Article : Google Scholar : PubMed/NCBI
275	Matsumoto KI, Yakumaru H, Narazaki M, Nakagawa H, Anzai K, Ikehira H and Ikota N: Modification of nitroxyl contrast agents with multiple spins and their proton T(1) relaxivity. Magn Reson Imaging. 26:117–121. 2008. View Article : Google Scholar
276	Benial AMF, Utsumi H, Ichikawa K, Murugesan R, Yamada K, Kinoshita Y, Naganuma T and Kato M: Dynamic nuclear polarization studies of redox-sensitive nitroxyl spin probes in liposomal solution. J Magn Reson. 204:131–138. 2010. View Article : Google Scholar : PubMed/NCBI
277	Yuan X, Yu H, Wang L, Uddin MA and Ouyang C: Nitroxide radical contrast agents for safe magnetic resonance imaging: Progress, challenges, and perspectives. Mater Horiz. 12:1726–1756. 2025. View Article : Google Scholar : PubMed/NCBI
278	Meenakumari V, Utsumi H, Jawahar A and Franklin Benial AM: Concentration dependence of nitroxyl spin probes in liposomal solution: Electron spin resonance and Overhauser-enhanced magnetic resonance studies. J Liposome Res. 28:87–96. 2018. View Article : Google Scholar
279	Yamada KI, Kinoshita Y, Yamasaki T, Sadasue H, Mito F, Nagai M, Matsumoto S, Aso M, Suemune H, Sakai K and Utsumi H: Synthesis of nitroxyl radicals for Overhauser-enhanced magnetic resonance imaging. Arch Pharm (Weinheim). 341:548–553. 2008. View Article : Google Scholar : PubMed/NCBI
280	Zhelev Z, Gadjeva V, Aoki I, Bakalova R and Saga T: Cell-penetrating nitroxides as molecular sensors for imaging of cancer in vivo, based on tissue redox activity. Mol Biosyst. 8:2733–2740. 2012. View Article : Google Scholar : PubMed/NCBI
281	Guo S, Wang X, Li Z, Pan D, Dai Y, Ye Y, Tian X, Gu Z, Gong Q, Zhang H and Luo K: A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence. J Nanobiotechnology. 19:2442021. View Article : Google Scholar : PubMed/NCBI
282	Nguyen HVT, Chen Q, Paletta JT, Harvey P, Jiang Y, Zhang H, Boska MD, Ottaviani MF, Jasanoff A, Rajca A and Johnson JA: Nitroxide-based macromolecular contrast agents with unprecedented transverse relaxivity and stability for magnetic resonance imaging of tumors. ACS Cent Sci. 3:800–811. 2017. View Article : Google Scholar : PubMed/NCBI
283	Guo S, Wang X, Dai Y, Dai X, Li Z, Luo Q, Zheng X, Gu Z, Zhang H, Gong Q and Luo K: Enhancing the efficacy of metal-free MRI contrast agents via conjugating nitroxides onto PEGylated cross-linked poly(carboxylate ester). Adv Sci (Weinh). 7:20004672020. View Article : Google Scholar : PubMed/NCBI
284	Wang X, Guo S, Li Z, Luo Q, Dai Y, Zhang H, Ye Y, Gong Q and Luo K: Amphiphilic branched polymer-nitroxides conjugate as a nanoscale agent for potential magnetic resonance imaging of multiple objects in vivo. J Nanobiotechnology. 19:2052021. View Article : Google Scholar : PubMed/NCBI
285	Niidome T, Gokuden R, Watanabe K, Mori T, Naganuma T, Utsumi H, Ichikawa K and Katayama Y: Nitroxyl radicals-modified dendritic poly (l-lysine) as a contrast agent for Overhauser-enhanced MRI. J Biomater Sci Polym Ed. 25:1425–1439. 2014. View Article : Google Scholar
286	Pinto LF, Lloveras V, Zhang S, Liko F, Veciana J, Muñoz-Gómez JL and Vidal-Gancedo J: Fully water-soluble polyphosphorhydrazone-based radical dendrimers functionalized with Tyr-PROXYL radicals as metal-free MRI T₁ contrast agents. ACS Appl Bio Mater. 3:369–376. 2020. View Article : Google Scholar : PubMed/NCBI
287	Wang X, Guo S, Li Z, Luo Q, Dai Y, Zhang H, Ye Y, Gong Q and Luo K: Amphiphilic branched polymer-nitroxides conjugate as a nanoscale agent for potential magnetic resonance imaging of multiple objects in vivo. J Nanobiotechnology. 19:2052021. View Article : Google Scholar : PubMed/NCBI
288	Zhang S, Lloveras V, Lope-Piedrafita S, Calero-Pérez P, Wu S, Candiota AP and Vidal-Gancedo J: Metal-free radical dendrimers as MRI contrast agents for glioblastoma diagnosis: Ex vivo and in vivo approaches. Biomacromolecules. 23:2767–2777. 2022. View Article : Google Scholar : PubMed/NCBI
289	Mitin D, Bullinger F, Dobrynin S, Engelmann J, Scheffler K, Kolokolov M, Krumkacheva O, Buckenmaier K, Kirilyuk I and Chubarov A: Contrast agents based on human serum albumin and nitroxides for ¹H-MRI and Overhauser-enhanced MRI. Int J Mol Sci. 25:40412024. View Article : Google Scholar
290	Tian C, Zhang S, Lloveras V and Gancedo JV: Application of radical dendrimers as organic radical contrast agents for magnetic resonance imaging. Adv Ind Eng Polym Res. 7:255–261. 2024.
291	Pagar RR, Musale SR, Pawar G, Kulkarni D and Giram PS: Comprehensive review on the degradation chemistry and toxicity studies of functional materials. ACS Biomater Sci Eng. 8:2161–2195. 2022. View Article : Google Scholar : PubMed/NCBI
292	Mellet P, Massot P, Madelin G, Marque SR, Harte E, Franconi JM and Thiaudière E: New concepts in molecular imaging: Non-invasive MRI spotting of proteolysis using an Overhauser effect switch. PLoS One. 4:e52442009. View Article : Google Scholar : PubMed/NCBI
293	Koonjoo N, Parzy E, Massot P, Lepetit-Coiffé M, Marque SR, Franconi JM, Thiaudiere E and Mellet P: In vivo Overhauser-enhanced MRI of proteolytic activity. Contrast Media Mol Imaging. 9:363–371. 2014. View Article : Google Scholar : PubMed/NCBI
294	Dobrynin S, Kutseikin S, Morozov D, Krumkacheva O, Spitsyna A, Gatilov Y, Silnikov V, Angelovski G, Bowman MK, Kirilyuk I and Chubarov A: Human serum albumin labelled with sterically-hindered nitroxides as potential MRI contrast agents. Molecules. 25:17092020. View Article : Google Scholar : PubMed/NCBI
295	Boudries D, Massot P, Parzy E, Seren S, Mellet P, Franconi JM, Miraux S, Bezançon E, Marque SRA, Audran G, et al: A system for in vivo on-demand ultra-low field Overhauser-enhanced 3D-magnetic resonance imaging. J Magn Reson. 348:1073832023. View Article : Google Scholar : PubMed/NCBI
296	Zhelev Z, Bakalova R, Aoki I, Matsumoto K, Gadjeva V, Anzai K and Kanno I: Nitroxyl radicals for labeling of conventional therapeutics and noninvasive magnetic resonance imaging of their permeability for blood-brain barrier: Relationship between structure, blood clearance, and MRI signal dynamic in the brain. Mol Pharm. 6:504–512. 2009. View Article : Google Scholar : PubMed/NCBI
297	Haugland MM, Lovett JE and Anderson EA: Advances in the synthesis of nitroxide radicals for use in biomolecule spin labelling. Chem Soc Rev. 47:668–680. 2018. View Article : Google Scholar
298	Akakuru OU, Iqbal MZ, Saeed M, Liu C, Paunesku T, Woloschak G, Hosmane NS and Wu A: The transition from metal-based to metal-free contrast agents for T₁ magnetic resonance imaging enhancement. Bioconjug Chem. 30:2264–2286. 2019. View Article : Google Scholar : PubMed/NCBI
299	Ding Y, Ge M, Zhang C, Yu J, Xia D, He J and Jia Z: Platelets as delivery vehicles for targeted enrichment of NO• to cerebral glioma for magnetic resonance imaging. J Nanobiotechnology. 21:4992023. View Article : Google Scholar
300	Brasch R: Work in progress: methods of contrast enhancement for NMR imaging and potential applications. A subject review. Radiology. 147:781–788. 1983. View Article : Google Scholar : PubMed/NCBI
301	Hou Y, Kong F, Tang Z, Zhang R, Li D, Ge J, Yu Z, Wahab A, Zhang Y, Iqbal MZ and Kong X: Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T₁-magnetic resonance imaging. J Control Release. 373:547–563. 2024. View Article : Google Scholar : PubMed/NCBI
302	Rohrer M, Bauer H, Mintorovitch J, Requardt M and Weinmann HJ: Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 40:715–724. 2005. View Article : Google Scholar : PubMed/NCBI
303	Xu W, Su Y, Ma Y, Wei Q, Yang J, Zhuang X, Ding J and Chen X: Immunologically effective poly (D-lactic acid) nanoparticle enhances anticancer immune response. Sci China Chem. 66:1150–1160. 2023. View Article : Google Scholar
304	Keana JF, Pou S and Rosen GM: Nitroxides as potential contrast enhancing agents for MRI application: Influence of structure on the rate of reduction by rat hepatocytes, whole liver homogenate, subcellular fractions, and ascorbate. Magn Reson Med. 5:525–536. 1987. View Article : Google Scholar : PubMed/NCBI
305	Muir BW, Acharya DP, Kennedy DF, Mulet X, Evans RA, Pereira SM, Wark KL, Boyd BJ, Nguyen TH, Hinton TM, et al: Metal-free and MRI visible theranostic lyotropic liquid crystal nitroxide-based nanoparticles. Biomaterials. 33:2723–2733. 2012. View Article : Google Scholar : PubMed/NCBI
306	Bye N, Hutt OE, Hinton TM, Acharya DP, Waddington LJ, Moffat BA, Wright DK, Wang HX, Mulet X and Muir BW: Nitroxide-loaded hexosomes provide MRI contrast in vivo. Langmuir. 30:8898–8906. 2014. View Article : Google Scholar : PubMed/NCBI
307	Chen C, Kang N, Xu T, Wang D, Ren L and Guo X: Core-shell hybrid upconversion nanoparticles carrying stable nitroxide radicals as potential multifunctional nanoprobes for upconversion luminescence and magnetic resonance dual-modality imaging. Nanoscale. 7:5249–5261. 2015. View Article : Google Scholar : PubMed/NCBI
308	Akakuru OU, Xu C, Liu C, Li Z, Xing J, Pan C, Li Y, Nosike EI, Zhang Z, Iqbal ZM, et al: Metal-free organo-theranostic nanosystem with high nitroxide stability and loading for image-guided targeted tumor therapy. ACS Nano. 15:3079–3097. 2021. View Article : Google Scholar : PubMed/NCBI
309	Utsumi H, Yamada KI, Ichikawa K, Sakai K, Kinoshita Y, Matsumoto S and Nagai M: Simultaneous molecular imaging of redox reactions monitored by Overhauser-enhanced MRI with 14N- and 15N-labeled nitroxyl radicals. Proc Natl Acad Sci USA. 103:1463–1468. 2006. View Article : Google Scholar : PubMed/NCBI
310	Letyagin AY, Sorokina KN, Tolstikova TG, Zhukova NA, Popova NA, Fursova EY, Savelov AA and Ovcharenko VI: Evaluation of magnetic resonance imaging characteristics of new nitroxyl radicals on the model of RLS lymphoma. Bull Exp Biol Med. 143:240–243. 2007. View Article : Google Scholar : PubMed/NCBI
311	Ahn KH, Scott G, Stang P, Conolly S and Hristov D: Multiparametric imaging of tumor oxygenation, redox status, and anatomical structure using Overhauser-enhanced MRI-prepolarized MRI system. Magn Reson Med. 65:1416–1422. 2011. View Article : Google Scholar : PubMed/NCBI
312	Parzy E, Bouchaud V, Massot P, Voisin P, Koonjoo N, Moncelet D, Franconi JM, Thiaudière E and Mellet P: Overhauser-enhanced MRI of elastase activity from in vitro human neutrophil degranulation. PLoS One. 8:e579462013. View Article : Google Scholar : PubMed/NCBI
313	Zhelev Z, Aoki I, Gadjeva V, Nikolova B, Bakalova R and Saga T: Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle. Eur J Cancer. 49:1467–1478. 2013. View Article : Google Scholar
314	Babić N, Orio M and Peyrot F: Unexpected rapid aerobic transformation of 2,2,6,6-tetraethyl-4-oxo(piperidin-1-yloxyl) radical by cytochrome P450 in the presence of NADPH: Evidence against a simple reduction of the nitroxide moiety to the hydroxylamine. Free Radic Biol Med. 156:144–156. 2020. View Article : Google Scholar
315	Maryunina K, Letyagin G, Romanenko G, Bogomyakov A, Morozov V, Tumanov S, Veber S, Fedin M, Saverina E, Syroeshkin M, et al: 2-imidazoline nitroxide derivatives of cymantrene. Molecules. 27:75452022. View Article : Google Scholar : PubMed/NCBI
316	Dobrynin SA, Gulman MM, Morozov DA, Zhurko IF, Taratayko AI, Sotnikova YS, Glazachev YI, Gatilov YV and Kirilyuk IA: Synthesis of sterically shielded nitroxides using the reaction of nitrones with alkynylmagnesium bromides. Molecules. 27:76262022. View Article : Google Scholar : PubMed/NCBI
317	Keshari KR and Wilson DM: Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev. 43:1627–1659. 2014. View Article : Google Scholar :
318	Woitek R and Gallagher FA: The use of hyperpolarised ¹³C-MRI in clinical body imaging to probe cancer metabolism. Br J Cancer. 124:1187–1198. 2021. View Article : Google Scholar : PubMed/NCBI
319	Ardenkjær-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M and Golman K: Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc Natl Acad Sci USA. 100:10158–10163. 2003. View Article : Google Scholar
320	Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI
321	Woitek R, McLean MA, Gill AB, Grist JT, Provenzano E, Patterson AJ, Ursprung S, Torheim T, Zaccagna F, Locke M, et al: Hyperpolarized ¹³C MRI of tumor metabolism demonstrates early metabolic response to neoadjuvant chemotherapy in breast cancer. Radiol Imaging Cancer. 2:e2000172020. View Article : Google Scholar
322	Gallagher FA, Woitek R, McLean MA, Gill AB, Manzano Garcia R, Provenzano E, Riemer F, Kaggie J, Chhabra A, Ursprung S, et al: Imaging breast cancer using hyperpolarized carbon-13 MRI. Proc Natl Acad Sci USA. 117:2092–2098. 2020. View Article : Google Scholar : PubMed/NCBI
323	Golman K, Zandt RI, Lerche M, Pehrson R and Ardenkjaer-Larsen JH: Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. Cancer Res. 66:10855–10860. 2006. View Article : Google Scholar : PubMed/NCBI
324	Miller JJ, Lau AZ, Nielsen PM, McMullen-Klein G, Lewis AJ, Jespersen NR, Ball V, Gallagher FA, Carr CA, Laustsen C, et al: Hyperpolarized [1,4-¹³C₂]fumarate enables magnetic resonance-based imaging of myocardial necrosis. JACC Cardiovasc Imaging. 11:1594–1606. 2018. View Article : Google Scholar :
325	Nelson SJ, Kurhanewicz J, Vigneron DB, Larson PE, Harzstark AL, Ferrone M, van Criekinge M, Chang JW, Bok R, Park I, et al: Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. Sci Transl Med. 5:198ra1082013. View Article : Google Scholar
326	Nantogma S, de Maissin H, Adelabu I, Abdurraheem A, Nelson C, Chukanov NV, Salnikov OG, Koptyug IV, Lehmkuhl S, Schmidt AB, et al: Carbon-13 radiofrequency amplification by stimulated emission of radiation of the hyperpolarized ketone and hemiketal forms of Allyl [1-¹³C]pyruvate. ACS Sens. 9:770–780. 2024. View Article : Google Scholar : PubMed/NCBI
327	Gierse M, Nagel L, Keim M, Lucas S, Speidel T, Lobmeyer T, Winter G, Josten F, Karaali S, Fellermann M, et al: Parahydrogen-polarized fumarate for preclinical in vivo metabolic magnetic resonance imaging. J Am Chem Soc. 145:5960–5969. 2023. View Article : Google Scholar : PubMed/NCBI
328	Cavallari E, Carrera C, Sorge M, Bonne G, Muchir A, Aime S and Reineri F: The ¹³C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time. Sci Rep. 8:83662018. View Article : Google Scholar
329	Bhattacharya P, Chekmenev EY, Reynolds WF, Wagner S, Zacharias N, Chan HR, Bünger R and Ross BD: Parahydrogen-induced polarization (PHIP) hyperpolarized MR receptor imaging in vivo: A pilot study of 13C imaging of atheroma in mice. NMR Biomed. 24:1023–1028. 2011. View Article : Google Scholar : PubMed/NCBI
330	Hövener JB, Pravdivtsev AN, Kidd B, Bowers CR, Glöggler S, Kovtunov KV, Plaumann M, Katz-Brull R, Buckenmaier K, Jerschow A, et al: Parahydrogen-based hyperpolarization for biomedicine. Angew Chem Int Ed Engl. 57:11140–11162. 2018. View Article : Google Scholar : PubMed/NCBI
331	Fries LM, Hune TLK, Sternkopf S, Mamone S, Schneider KL, Schulz-Heddergott R, Becker D and Glöggler S: Real-time metabolic magnetic resonance spectroscopy of pancreatic and colon cancer tumor-xenografts with parahydrogen hyperpolarized 1-¹³C Pyruvate-d₃. Chemistry. 30:e2024001872024. View Article : Google Scholar
332	Shchepin RV, Pham W and Chekmenev EY: Dephosphorylation and biodistribution of 1-¹³C-phospholactate in vivo. J Labelled Comp Radiopharm. 57:517–524. 2014. View Article : Google Scholar : PubMed/NCBI
333	Chaumeil MM, Larson PE, Yoshihara HA, Danforth OM, Vigneron DB, Nelson SJ, Pieper RO, Phillips JJ and Ronen SM: Non-invasive in vivo assessment of IDH1 mutational status in glioma. Nat Commun. 4:24292013. View Article : Google Scholar : PubMed/NCBI
334	Canapè C, Catanzaro G, Terreno E, Karlsson M, Lerche MH and Jensen PR: Probing treatment response of glutaminolytic prostate cancer cells to natural drugs with hyperpolarized [5-(13) C] glutamine. Magn Reson Med. 73:2296–2305. 2015. View Article : Google Scholar
335	Mu C, Liu X, Kim Y, Riselli A, Korenchan DE, Bok RA, Delos Santos R, Sriram R, Qin H, Nguyen H, et al: Clinically translatable hyperpolarized ¹³C bicarbonate pH imaging method for use in prostate cancer. ACS Sens. 8:4042–4054. 2023. View Article : Google Scholar : PubMed/NCBI
336	Düwel S, Hundshammer C, Gersch M, Feuerecker B, Steiger K, Buck A, Walch A, Haase A, Glaser SJ, Schwaiger M and Schilling F: Imaging of pH in vivo using hyperpolarized ¹³C-labelled zymonic acid. Nat Commun. 8:151262017. View Article : Google Scholar
337	Coffey AM, Feldman MA, Shchepin RV, Barskiy DA, Truong ML, Pham W and Chekmenev EY: High-resolution hyperpolarized in vivo metabolic ¹³C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection. J Magn Reson. 281:246–252. 2017. View Article : Google Scholar : PubMed/NCBI
338	Park I, von Morze C, Lupo JM, Ardenkjaer-Larsen JH, Kadambi A, Vigneron DB and Nelson SJ: Investigating tumor perfusion by hyperpolarized ¹³C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts. Magn Reson Med. 77:841–847. 2017. View Article : Google Scholar
339	Von Morze C, Larson PEZ, Hu S, Yoshihara HA, Bok RA, Goga A, Ardenkjaer-Larsen JH and Vigneron DB: Investigating tumor perfusion and metabolism using multiple hyperpolarized (13)C compounds: HP001, pyruvate and urea. Magn Reson Imaging. 30:305–311. 2012. View Article : Google Scholar
340	Von Morze C, Bok RA, Reed GD, Ardenkjaer-Larsen JH, Kurhanewicz J and Vigneron DB: Simultaneous multiagent hyperpolarized (13)C perfusion imaging. Magn Reson Med. 72:1599–1609. 2014. View Article : Google Scholar : PubMed/NCBI
341	Laustsen C, Nielsen PM, Qi H, Løbner MH, Palmfeldt J and Bertelsen LB: Hyperpolarized [1,4-¹³C]fumarate imaging detects microvascular complications and hypoxia mediated cell death in diabetic nephropathy. Sci Rep. 10:96502020. View Article : Google Scholar
342	Schmidt AB, Berner S, Braig M, Zimmermann M, Hennig J, von Elverfeldt D and Hövener JB: In vivo 13C-MRI using SAMBADENA. PLoS One. 13:e02001412018. View Article : Google Scholar : PubMed/NCBI
343	Svensson J, Månsson S, Johansson E, Petersson JS and Olsson LE: Hyperpolarized 13C MR angiography using trueFISP. Magn Reson Med. 50:256–262. 2003. View Article : Google Scholar : PubMed/NCBI
344	Allouche-Arnon H, Wade T, Waldner LF, Miller VN, Gomori JM, Katz-Brull R and McKenzie CA: In vivo magnetic resonance imaging of glucose-initial experience. Contrast Media Mol Imaging. 8:72–82. 2013. View Article : Google Scholar
345	Flori A, Liserani M, Frijia F, Giovannetti G, Lionetti V, Casieri V, Positano V, Aquaro GD, Recchia FA, Santarelli MF, et al: Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model. Contrast Media Mol Imaging. 10:194–202. 2015. View Article : Google Scholar
346	Magnusson P, Johansson E, Månsson S, Petersson JS, Chai CM, Hansson G, Axelsson O and Golman K: Passive catheter tracking during interventional MRI using hyperpolarized 13C. Magn Reson Med. 57:1140–1147. 2007. View Article : Google Scholar : PubMed/NCBI
347	McBride SJ, MacCulloch K, TomHon P, Browning A, Meisel S, Abdulmojeed M, Goodson BM, Chekmenev EY and Theis T: Carbon-13 hyperpolarization of α-ketocarboxylates with parahydrogen in reversible exchange. CChemMedChem. 20:e2024003782025. View Article : Google Scholar
348	Roig ES, Magill AW, Donati G, Meyerspeer M, Xin L, Ipek O and Gruetter R: A double-quadrature radiofrequency coil design for proton-decoupled carbon-13 magnetic resonance spectroscopy in humans at 7T. Magn Reson Med. 73:894–900. 2015. View Article : Google Scholar
349	Von Morze C, Tropp J, Chen AP, Marco-Rius I, Van Criekinge M, Skloss TW, Mammoli D, Kurhanewicz J, Vigneron DB, Ohliger MA and Merritt ME: Sensitivity enhancement for detection of hyperpolarized ¹³C MRI probes with ¹H spin coupling introduced by enzymatic transformation in vivo. Magn Reson Med. 80:36–41. 2018. View Article : Google Scholar
350	Chapman B, Joalland B, Meersman C, Ettedgui J, Swenson RE, Krishna MC, Nikolaou P, Kovtunov KV, Salnikov OG, Koptyug IV, et al: Low-cost high-pressure clinical-scale 50% parahydrogen generator using liquid nitrogen at 77 K. Anal Chem. 93:8476–8483. 2021. View Article : Google Scholar : PubMed/NCBI
351	Schmidt AB, Zimmermann M, Berner S, de Maissin H, Müller CA, Ivantaev V, Hennig J, Elverfeldt DV and Hövener JB: Quasi-continuous production of highly hyperpolarized carbon-13 contrast agents every 15 sec within an MRI system. Commun Chem. 5:212022. View Article : Google Scholar
352	Shchepi n RV, Coffey AM, Waddell K and Wand Chekmenev EY: Parahydrogen induced polarization of 1-(13)C-phospholactate-d(2) for biomedical imaging with >30,000,000-fold NMR signal enhancement in water. Anal Chem. 86:5601–5605. 2014. View Article : Google Scholar
353	Johansson E, Månsson S, Wirestam R, Svensson J, Petersson JS, Golman K and Ståhlberg F: Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C. Magn Reson Med. 51:464–472. 2004. View Article : Google Scholar : PubMed/NCBI
354	Grant AK, Vinogradov E, Wang X, Lenkinski RE and Alsop DC: Perfusion imaging with a freely diffusible hyperpolarized contrast agent. Magn Reson Med. 66:746–755. 2011. View Article : Google Scholar : PubMed/NCBI
355	Allouche-Arnon H, Gamliel A, Barzilay CM, Nalbandian R, Gomori JM, Karlsson M, Lerche MH and Katz-Brull R: A hyperpolarized choline molecular probe for monitoring acetylcholine synthesis. Contrast Media Mol Imaging. 6:139–147. 2011. View Article : Google Scholar : PubMed/NCBI
356	Coffey AM, Shchepin RV, Truong ML, Wilkens K, Pham W and Chekmenev EY: Open-source automated parahydrogen hyperpolarizer for molecular imaging using (13)C metabolic contrast agents. Anal Chem. 88:8279–8288. 2016. View Article : Google Scholar : PubMed/NCBI
357	Qi H, Mariager CØ, Nielsen PM, Schroeder M, Lindhardt J, Nørregaard R, Klein JD, Sands JM and Laustsen C: Glucagon infusion alters the hyperpolarized ¹³C-urea renal hemodynamic signature. NMR Biomed. 32:e40282019. View Article : Google Scholar
358	Colombo Serra S, Karlsson M, Giovenzana GB, Cavallotti C, Tedoldi F and Aime S: Hyperpolarized (13) C-labelled anhydrides as DNP precursors of metabolic MRI agents. Contrast Media Mol Imaging. 7:469–477. 2012. View Article : Google Scholar : PubMed/NCBI
359	Coffey AM, Kovtunov KV, Barskiy DA, Koptyug IV, Shchepin RV, Waddell KW, He P, Groome KA, Best QA, Shi F, et al: High-resolution low-field molecular magnetic resonance imaging of hyperpolarized liquids. Anal Chem. 86:9042–9049. 2014. View Article : Google Scholar : PubMed/NCBI
360	Waddell KW, Coffey AM and Chekmenev EY: In situ detection of PHIP at 48 mT: Demonstration using a centrally controlled polarizer. J Am Chem Soc. 133:97–101. 2011. View Article : Google Scholar :
361	Roth M, Koch A, Kindervater P, Bargon J, Spiess HW and Münnemann K: (13)C hyperpolarization of a barbituric acid derivative via parahydrogen induced polarization. J Magn Reson. 204:50–55. 2010. View Article : Google Scholar : PubMed/NCBI
362	Berner S, Schmidt AB, Zimmermann M, Pravdivtsev AN, Glöggler S, Hennig J, von Elverfeldt D and Hövener JB: SAMBADENA hyperpolarization of ¹³C-succinate in an MRI: Singlet-triplet mixing causes polarization loss. ChemistryOpen. 8:728–736. 2019. View Article : Google Scholar : PubMed/NCBI
363	Deen SS, Rooney C, Shinozaki A, McGing J, Grist JT, Tyler DJ, Serrão E and Gallagher FA: Hyperpolarized carbon 13 MRI: Clinical applications and future directions in oncology. Radiol Imaging Cancer. 5:e2300052023. View Article : Google Scholar : PubMed/NCBI
364	Vinogradov E, Keupp J, Dimitrov IE, Seiler S and Pedrosa I: CEST-MRI for body oncologic imaging: Are we there yet? NMR Biomed. 36:e49062023. View Article : Google Scholar : PubMed/NCBI