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Prognostic Value of Fluorine-19 MRI Oximetry Monitoring in cancer

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A Correction to this article was published on 30 November 2021

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Abstract

Hypoxia is a key prognostic indicator in most solid tumors, as it is correlated to tumor angiogenesis, metastasis, recurrence, and response to therapy. Accurate measurement and mapping of tumor oxygenation profile and changes upon intervention could facilitate disease progression assessment and assist in treatment planning. Currently, no gold standard exists for non-invasive spatiotemporal measurement of hypoxia. Magnetic resonance imaging (MRI) represents an attractive option as it is a clinically available and non-ionizing imaging modality. Specifically, perfluorocarbon (PFC) beacons can be externally introduced into the tumor tissue and the linear dependence of their spin-lattice relaxation rate (R1) on the local partial pressure of oxygen (pO2) exploited for real-time tissue oxygenation monitoring in vivo. In this review, we will focus on early studies and recent developments of fluorine-19 MRI and spectroscopy (MRS) for evaluation of tumor oximetry and response to therapy.

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References

  1. Buttgereit F, Brand MD (1995) A hierarchy of ATP-consuming processes in mammalian cells. Biochem J 312(Pt 1):163–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Carreau A, El Hafny-Rahbi B, Matejuk A, Grillon C, Kieda C (2011) Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med 15:1239–1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Feldman JL, Mitchell GS, Nattie EE (2003) Breathing: rhythmicity, plasticity, chemosensitivity. Annu Rev Neurosci 26:239–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ortiz-Prado E, Dunn JF, Vasconez J, Castillo D, Viscor G (2019) Partial pressure of oxygen in the human body: a general review. Am J Blood Res 9:1–14

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Clifford PS, Hellsten Y (2004) Vasodilatory mechanisms in contracting skeletal muscle. J Appl Physiol (1985) 97:393–403

    Article  Google Scholar 

  6. Jernigan NL, Drummond HA (2005) Vascular ENaC proteins are required for renal myogenic constriction. Am J Physiol Ren Physiol 289:F891–F901

    Article  CAS  Google Scholar 

  7. Dings J, Meixensberger J, Jager A, Roosen K (1998) Clinical experience with 118 brain tissue oxygen partial pressure catheter probes. Neurosurgery 43:1082–1095

    Article  CAS  PubMed  Google Scholar 

  8. Harrison JS, Rameshwar P, Chang V, Bandari P (2002) Oxygen saturation in the bone marrow of healthy volunteers. Blood 99:394

    Article  CAS  PubMed  Google Scholar 

  9. Leary TS, Klinck JR, Hayman G, Friend P, Jamieson NV, Gupta AK (2002) Measurement of liver tissue oxygenation after orthotopic liver transplantation using a multiparameter sensor. A pilot study. Anaesthesia 57:1128–1133

    Article  CAS  PubMed  Google Scholar 

  10. Richardson RS, Duteil S, Wary C, Wray DW, Hoff J, Carlier PG (2006) Human skeletal muscle intracellular oxygenation: the impact of ambient oxygen availability. J Physiol 571:415–424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Muz B, de la Puente P, Azab F, Azab AK (2015) The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl) 3:83–92

    Article  Google Scholar 

  12. Vaupel P, Mayer A, Hockel M (2004) Tumor hypoxia and malignant progression. Methods Enzymol 381:335–354

    Article  CAS  PubMed  Google Scholar 

  13. Krogh A (1922) The anatomy and physiology of capillaries. Yale University press, Yale

    Google Scholar 

  14. Vaupel P, Briest S, Hockel M (2002) Hypoxia in breast cancer: pathogenesis, characterization and biological/therapeutic implications. Wien Med Wochenschr 152:334–342

    Article  CAS  PubMed  Google Scholar 

  15. Carmeliet P, Jain RK (2011) Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov 10:417–427

    Article  CAS  PubMed  Google Scholar 

  16. Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL (2000) Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A 97:14608–14613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Brown EB, Campbell RB, Tsuzuki Y, Xu L, Carmeliet P, Fukumura D, Jain RK (2001) In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat Med 7:864–868

    Article  CAS  PubMed  Google Scholar 

  18. Evans SM, Jenkins WT, Shapiro M, Koch CJ (1997) Evaluation of the concept of “hypoxic fraction” as a descriptor of tumor oxygenation status. Adv Exp Med Biol 411:215–225

    Article  CAS  PubMed  Google Scholar 

  19. Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941–943

    CAS  PubMed  Google Scholar 

  20. Hockel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93:266–276

    Article  CAS  PubMed  Google Scholar 

  21. Nordsmark M, Bentzen SM, Rudat V, Brizel D, Lartigau E, Stadler P, Becker A, Adam M, Molls M, Dunst J, Terris DJ, Overgaard J (2005) Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol 77:18–24

    Article  PubMed  Google Scholar 

  22. Hockel M, Vaupel P (2001) Biological consequences of tumor hypoxia. Semin Oncol 28:36–41

    Article  CAS  PubMed  Google Scholar 

  23. Brown JM, Giaccia AJ (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 58:1408–1416

    CAS  PubMed  Google Scholar 

  24. Tatum JL, Kelloff GJ, Gillies RJ, Arbeit JM, Brown JM, Chao KS, Chapman JD, Eckelman WC, Fyles AW, Giaccia AJ, Hill RP, Koch CJ, Krishna MC, Krohn KA, Lewis JS, Mason RP, Melillo G, Padhani AR, Powis G, Rajendran JG, Reba R, Robinson SP, Semenza GL, Swartz HM, Vaupel P, Yang D, Croft B, Hoffman J, Liu G, Stone H, Sullivan D (2006) Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int J Radiat Biol 82:699–757

    Article  CAS  PubMed  Google Scholar 

  25. Walsh JC, Lebedev A, Aten E, Madsen K, Marciano L, Kolb HC (2014) The clinical importance of assessing tumor hypoxia: relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid Redox Signal 21:1516–1554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Thompson KE, Royds JA (1999) Hypoxia and reoxygenation: a pressure for mutant p53 cell selection and tumour progression. Bull Math Biol 61:759–778

    Article  CAS  PubMed  Google Scholar 

  27. Semenza GL (2000) Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 35:71–103

    Article  CAS  PubMed  Google Scholar 

  28. Young SD, Marshall RS, Hill RP (1988) Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc Natl Acad Sci U S A 85:9533–9537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sundfor K, Lyng H, Rofstad EK (1998) Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 78:822–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hickman JA, Potten CS, Merritt AJ, Fisher TC (1994) Apoptosis and cancer chemotherapy. Philos Trans R Soc Lond Ser B Biol Sci 345:319–325

    Article  CAS  Google Scholar 

  31. Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C, Chilvers ER, Dransfield I, Donnelly SC, Strieter R, Haslett C (1999) Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med 5:662–668

    Article  CAS  PubMed  Google Scholar 

  32. Zhivotovsky B, Joseph B, Orrenius S (1999) Tumor radiosensitivity and apoptosis. Exp Cell Res 248:10–17

    Article  CAS  PubMed  Google Scholar 

  33. Bedford JS, Mitchell JB (1974) The effect of hypoxia on the growth and radiation response of mammalian cells in culture. Br J Radiol 47:687–696

    Article  CAS  PubMed  Google Scholar 

  34. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648

    Article  CAS  PubMed  Google Scholar 

  35. Chapman JD (1991) Measurement of tumor hypoxia by invasive and non-invasive procedures: a review of recent clinical studies. Radiother Oncol 20(Suppl 1):13–19

    Article  PubMed  Google Scholar 

  36. Mason RP, Zhao D, Pacheco-Torres J, Cui W, Kodibagkar VD, Gulaka PK, Hao G, Thorpe P, Hahn EW, Peschke P (2010) Multimodality imaging of hypoxia in preclinical settings. Q J Nucl Med Mol Imaging 54:259–280

    CAS  PubMed  PubMed Central  Google Scholar 

  37. D'Alonzo RA, Gill S, Rowshanfarzad P et al (2021) In vivo noninvasive preclinical tumor hypoxia imaging methods: a review. Int J Radiat Biol 97:593–631

    Article  CAS  PubMed  Google Scholar 

  38. Nordsmark M, Bentzen SM, Overgaard J (1994) Measurement of human tumour oxygenation status by a polarographic needle electrode. An analysis of inter- and intratumour heterogeneity. Acta Oncol 33:383–389

    Article  CAS  PubMed  Google Scholar 

  39. Lumb AB, Horncastle E (2019) Pharmacology and physiology for anesthesia : foundations and clinical Application. Ed. Elsevier

  40. Yeh KA, Biade S, Lanciano RM, Brown DQ, Fenning MC, Babb JS, Hanks GE, Chapman JD (1995) Polarographic needle electrode measurements of oxygen in rat prostate carcinomas: accuracy and reproducibility. Int J Radiat Oncol Biol Phys 33:111–118

    Article  CAS  PubMed  Google Scholar 

  41. Varia MA, Calkins-Adams DP, Rinker LH, Kennedy AS, Novotny DB, Fowler WC Jr, Raleigh JA (1998) Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecol Oncol 71:270–277

    Article  CAS  PubMed  Google Scholar 

  42. Aguilera KY, Brekken RA (2014) Hypoxia studies with pimonidazole in vivo. Bio Protoc 4:e1254

    Article  PubMed  Google Scholar 

  43. Chapman JD, Franko AJ, Sharplin J (1981) A marker for hypoxic cells in tumours with potential clinical applicability. Br J Cancer 43:546–550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rasey JS, Grunbaum Z, Magee S, Nelson NJ, Olive PL, Durand RE, Krohn KA (1987) Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. Radiat Res 111:292–304

    Article  CAS  PubMed  Google Scholar 

  45. Krohn KA, Link JM, Mason RP (2008) Molecular imaging of hypoxia. J Nucl Med 49(Suppl 2):129S–148S

    Article  CAS  PubMed  Google Scholar 

  46. Vanderkooi JM, Wilson DF (1986) A new method for measuring oxygen concentration in biological systems. Adv Exp Med Biol 200:189–193

    Article  CAS  PubMed  Google Scholar 

  47. Rumsey WL, Vanderkooi JM, Wilson DF (1988) Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue. Science 241:1649–1651

    Article  CAS  PubMed  Google Scholar 

  48. Liu H, Song Y, Worden KL, Jiang X, Constantinescu A, Mason RP (2000) Noninvasive investigation of blood oxygenation dynamics of tumors by near-infrared spectroscopy. Appl Opt 39:5231–5243

    Article  CAS  PubMed  Google Scholar 

  49. Kuppusamy P, Afeworki M, Shankar RA, Coffin D, Krishna MC, Hahn SM, Mitchell JB, Zweier JL (1998) In vivo electron paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model. Cancer Res 58:1562–1568

    CAS  PubMed  Google Scholar 

  50. Gallez B, Baudelet C, Jordan BF (2004) Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications. NMR Biomed 17:240–262

    Article  CAS  PubMed  Google Scholar 

  51. Choyke PL, Dwyer AJ, Knopp MV (2003) Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging. J Magn Reson Imaging 17:509–520

    Article  PubMed  Google Scholar 

  52. Chopra S, Foltz WD, Milosevic MF, Toi A, Bristow RG, Ménard C, A. Haider M (2009) Comparing oxygen-sensitive MRI (BOLD R2*) with oxygen electrode measurements: a pilot study in men with prostate cancer. Int J Radiat Biol 85:805–813

    Article  CAS  PubMed  Google Scholar 

  53. Bourke VA, Zhao D, Gilio J, Chang CH, Jiang L, Hahn EW, Mason RP (2007) Correlation of radiation response with tumor oxygenation in the Dunning prostate R3327-AT1 tumor. Int J Radiat Oncol Biol Phys 67:1179–1186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hoskin PJ, Carnell DM, Taylor NJ, Smith RE, Stirling JJ, Daley FM, Saunders MI, Bentzen SM, Collins DJ, d’Arcy JA, Padhani AP (2007) Hypoxia in prostate cancer: correlation of BOLD-MRI with pimonidazole immunohistochemistry-initial observations. Int J Radiat Oncol Biol Phys 68:1065–1071

    Article  CAS  PubMed  Google Scholar 

  55. Riess JG (2001) Oxygen carriers (“blood substitutes”)--raison d’etre, chemistry, and some physiology. Chem Rev 101:2797–2920

    Article  CAS  PubMed  Google Scholar 

  56. Riess JG (2005) Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artif Cells Blood Substit Immobil Biotechnol 33:47–63

    Article  CAS  PubMed  Google Scholar 

  57. Riess JG, Le Blanc M (1978) Perfluoro compounds as blood substitutes. Angew Chem Int Ed Eng 17:621–634

    Article  CAS  Google Scholar 

  58. Delpuech JJ, Hamza MA, Serratrice G, Stébé MJ (1979) Fluorocarbons as oxygen carriers. I An NMR study of oxygen solutions in hexafluorobenzene. J Chem Phys 70:2680–2687

    Article  CAS  Google Scholar 

  59. Delpuech JJ, Hamza MA, Serratrice G (1979) Determination of oxygen by a nuclear magnetic-resonance method. J Magn Reson 36:173–179

    CAS  Google Scholar 

  60. Mason RP, Shukla H, Antich PP (1993) In vivo oxygen tension and temperature: simultaneous determination using 19F NMR spectroscopy of perfluorocarbon. Magn Reson Med 29:296–302

    Article  CAS  PubMed  Google Scholar 

  61. Noth U, Morrissey SP, Deichmann R et al (1995) In vivo measurement of partial oxygen pressure in large vessels and in the reticuloendothelial system using fast 19F-MRI. Magn Reson Med 34:738–745

    Article  CAS  PubMed  Google Scholar 

  62. Mason RP, Nunnally RL, Antich PP (1991) Tissue oxygenation: a novel determination using 19F surface coil NMR spectroscopy of sequestered perfluorocarbon emulsion. Magn Reson Med 18:71–79

    Article  CAS  PubMed  Google Scholar 

  63. Dardzinski BJ, Sotak CH (1994) Rapid tissue oxygen tension mapping using 19F inversion-recovery echo-planar imaging of perfluoro-15-crown-5-ether. Magn Reson Med 32:88–97

    Article  CAS  PubMed  Google Scholar 

  64. Sotak CH, Hees PS, Huang HN, Hung MH, Krespan CG, Raynolds S (1993) A new perfluorocarbon for use in fluorine-19 magnetic resonance imaging and spectroscopy. Magn Reson Med 29:188–195

    Article  CAS  PubMed  Google Scholar 

  65. Winter PM, Cai K, Caruthers SD, Wickline SA, Lanza GM (2007) Emerging nanomedicine opportunities with perfluorocarbon nanoparticles. Expert Rev Med Devices 4:137–145

    Article  CAS  PubMed  Google Scholar 

  66. Mason RP, Antich PP, Babcock EE, Constantinescu A, Peschke P, Hahn EW (1994) Non-invasive determination of tumor oxygen tension and local variation with growth. Int J Radiat Oncol Biol Phys 29:95–103

    Article  CAS  PubMed  Google Scholar 

  67. Song Y, Constantinescu A, Mason RP (2002) Dynamic breast tumor oximetry: the development of prognostic radiology. Technol Cancer Res Treat 1:471–478

    Article  PubMed  Google Scholar 

  68. Zhao D, Ran S, Constantinescu A, Hahn EW, Mason RP (2003) Tumor oxygen dynamics: correlation of in vivo MRI with histological findings. Neoplasia 5:308–318

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zhao D, Constantinescu A, Chang CH, Hahn EW, Mason RP (2003) Correlation of tumor oxygen dynamics with radiation response of the dunning prostate R3327-HI tumor. Radiat Res 159:621–631

    Article  CAS  PubMed  Google Scholar 

  70. Mishima H, Kobayashi T, Shimizu M, Tamaki Y, Baba M, Shimano T, Itoh S, Yamazaki M, Iriguchi N, Takahashi M, Mori T (1991) In vivo F-19 chemical shift imaging with FTPA and antibody-coupled FMIQ. J Magn Reson Imaging 1:705–709

    Article  CAS  PubMed  Google Scholar 

  71. Zhao D, Constantinescu A, Hahn EW, Mason RP (2001) Tumor oxygen dynamics with respect to growth and respiratory challenge: investigation of the Dunning prostate R3327-HI tumor. Radiat Res 156:510–520

    Article  CAS  PubMed  Google Scholar 

  72. Zhao D, Jiang L, Hahn EW, Mason RP (2005) Tumor physiologic response to combretastatin A4 phosphate assessed by MRI. Int J Radiat Oncol Biol Phys 62:872–880

    Article  CAS  PubMed  Google Scholar 

  73. Mason RP, Constantinescu A, Hunjan S, le D, Hahn EW, Antich PP, Blum C, Peschke P (1999) Regional tumor oxygenation and measurement of dynamic changes. Radiat Res 152:239–249

    Article  CAS  PubMed  Google Scholar 

  74. Liu S, Shah SJ, Wilmes LJ, Feiner J, Kodibagkar VD, Wendland MF, Mason RP, Hylton N, Hopf HW, Rollins MD (2011) Quantitative tissue oxygen measurement in multiple organs using 19F MRI in a rat model. Magn Reson Med 66:1722–1730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chapelin F, Leach BI, Chen R, Lister D, Messer K, Okada H, Ahrens ET (2021) Assessing oximetry response to chimeric antigen receptor T-cell therapy against glioma with (19)F MRI in a murine model. Radiol Imaging Cancer 3:e200062

    Article  PubMed  PubMed Central  Google Scholar 

  76. Kegel S, Chacon-Caldera J, Tsagogiorgas C, Theisinger B, Glatting G, Schad LR (2016) (19)F Oximetry with semifluorinated alkanes. Artif Cells Nanomed Biotechnol 44:1861–1866

    Article  CAS  PubMed  Google Scholar 

  77. Kadayakkara DK, Damodaran K, Hitchens TK, Bulte JW, Ahrens ET (2014) (19)F spin-lattice relaxation of perfluoropolyethers: dependence on temperature and magnetic field strength (7.0-14.1T). J Magn Reson 242:18–22

    Article  CAS  PubMed  Google Scholar 

  78. Spanoudaki V, Doloff JC, Huang W, Norcross SR, Farah S, Langer R, Anderson DG (2019) Simultaneous spatiotemporal tracking and oxygen sensing of transient implants in vivo using hot-spot MRI and machine learning. Proc Natl Acad Sci U S A 116:4861–4870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Somanchi SS, Kennis BA, Gopalakrishnan V, Lee DA, Bankson JA (2016) In vivo (19)F-magnetic resonance imaging of adoptively transferred NK cells. Methods Mol Biol 1441:317–332

    Article  CAS  PubMed  Google Scholar 

  80. Ku MC, Edes I, Bendix I, Pohlmann A, Waiczies H, Prozorovski T, Günther M, Martin C, Pagès G, Wolf SA, Kettenmann H, Uckert W, Niendorf T, Waiczies S (2016) ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas. Mol Cancer Ther 15:1975–1987

    Article  CAS  PubMed  Google Scholar 

  81. McFarland E, Koutcher JA, Rosen BR, Teicher B, Brady TJ (1985) In vivo 19F NMR imaging. J Comput Assist Tomogr 9:8–15

    Article  CAS  PubMed  Google Scholar 

  82. Mason RP, Antich PP, Babcock EE, Gerberich JL, Nunnally RL (1989) Perfluorocarbon imaging in vivo: a 19F MRI study in tumor-bearing mice. Magn Reson Imaging 7:475–485

    Article  CAS  PubMed  Google Scholar 

  83. Mason RP, Rodbumrung W, Antich PP (1996) Hexafluorobenzene: a sensitive 19F NMR indicator of tumor oxygenation. NMR Biomed 9:125–134

    Article  CAS  PubMed  Google Scholar 

  84. Janjic JM, Srinivas M, Kadayakkara DK, Ahrens ET (2008) Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection. J Am Chem Soc 130:2832–2841

    Article  CAS  PubMed  Google Scholar 

  85. Zhong J, Sakaki M, Okada H, Ahrens ET (2013) In vivo intracellular oxygen dynamics in murine brain glioma and immunotherapeutic response of cytotoxic T cells observed by fluorine-19 magnetic resonance imaging. PLoS One 8:e59479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kadayakkara DK, Janjic JM, Pusateri LK, Young WB, Ahrens ET (2010) In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI. Magn Reson Med 64:1252–1259

    Article  PubMed  PubMed Central  Google Scholar 

  87. Kadayakkara DK, Ranganathan S, Young WB, Ahrens ET (2012) Assaying macrophage activity in a murine model of inflammatory bowel disease using fluorine-19 MRI. Lab Investig 92:636–645

    Article  CAS  PubMed  Google Scholar 

  88. Holland GNBP, Hinshaw WS (1977) 19F magnetic resonance imaging. J Magn Reson 28:133–136

    CAS  Google Scholar 

  89. Joseph PM, Fishman JE (1985) Design and evaluation of a radio frequency coil for nuclear magnetic resonance imaging of fluorine and protons. Med Phys 12:679–683

    Article  CAS  PubMed  Google Scholar 

  90. Parhami P, Fung BM (1983) Fluorine-19 relaxation study of perfluoro chemicals as oxygen carriers. J Phys Chem 87:1928–1931

    Article  CAS  Google Scholar 

  91. Clark LC Jr, Ackerman JL, Thomas SR et al (1984) Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen. Adv Exp Med Biol 180:835–845

    Article  CAS  PubMed  Google Scholar 

  92. Hunjan S, Zhao D, Constantinescu A, Hahn EW, Antich PP, Mason RP (2001) Tumor oximetry: demonstration of an enhanced dynamic mapping procedure using fluorine-19 echo planar magnetic resonance imaging in the Dunning prostate R3327-AT1 rat tumor. Int J Radiat Oncol Biol Phys 49:1097–1108

    Article  CAS  PubMed  Google Scholar 

  93. Zhao D, Constantinescu A, Hahn EW, Mason RP (2002) Differential oxygen dynamics in two diverse Dunning prostate R3327 rat tumor sublines (MAT-Lu and HI) with respect to growth and respiratory challenge. Int J Radiat Oncol Biol Phys 53:744–756

    Article  PubMed  Google Scholar 

  94. Zhao D, Jiang L, Hahn EW, Mason RP (2009) Comparison of 1H blood oxygen level-dependent (BOLD) and 19F MRI to investigate tumor oxygenation. Magn Reson Med 62:357–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Hees PS, Sotak CH (1993) Assessment of changes in murine tumor oxygenation in response to nicotinamide using 19F NMR relaxometry of a perfluorocarbon emulsion. Magn Reson Med 29:303–310

    Article  CAS  PubMed  Google Scholar 

  96. Horsman MR, Chaplin DJ, Brown JM (1989) Tumor radiosensitization by nicotinamide: a result of improved perfusion and oxygenation. Radiat Res 118:139–150

    Article  CAS  PubMed  Google Scholar 

  97. Fink C, Gaudet JM, Fox MS et al (2018) (19)F-perfluorocarbon-labeled human peripheral blood mononuclear cells can be detected in vivo using clinical MRI parameters in a therapeutic cell setting. Sci Rep 8:590

    Article  PubMed  PubMed Central  Google Scholar 

  98. Bouchlaka MN, Ludwig KD, Gordon JW et al (2016) (19)F-MRI for monitoring human NK cells in vivo. Oncoimmunology 5:e1143996

    Article  PubMed  PubMed Central  Google Scholar 

  99. Boehm-Sturm P, Mueller S, Freitag N, Borowski S, Foddis M, Koch SP, Temme S, Flögel U, Blois SM (2021) Phenotyping placental oxygenation in Lgals1 deficient mice using (19)F MRI. Sci Rep 11:2126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Simkins JW, Stewart PS, Codd SL, Seymour JD (2019) Non-invasive imaging of oxygen concentration in a complex in vitro biofilm infection model using (19) F MRI: persistence of an oxygen sink despite prolonged antibiotic therapy. Magn Reson Med 82:2248–2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Mastropietro A, De Bernardi E, Breschi GL et al (2014) Optimization of rapid acquisition with relaxation enhancement (RARE) pulse sequence parameters for (1)(9)F-MRI studies. J Magn Reson Imaging 40:162–170

    Article  PubMed  Google Scholar 

  102. Ribot EJ, Gaudet JM, Chen Y, Gilbert KM, Foster PJ (2014) In vivo MR detection of fluorine-labeled human MSC using the bSSFP sequence. Int J Nanomedicine 9:1731–1739

    Article  PubMed  PubMed Central  Google Scholar 

  103. Ghuman H, Hitchens TK, Modo M (2019) A systematic optimization of (19)F MR image acquisition to detect macrophage invasion into an ECM hydrogel implanted in the stroke-damaged brain. Neuroimage 202:116090

    Article  CAS  PubMed  Google Scholar 

  104. Ahrens ET, Bulte JW (2013) Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol 13:755–763

    Article  CAS  PubMed  Google Scholar 

  105. Zhong J, Mills PH, Hitchens TK, Ahrens ET (2013) Accelerated fluorine-19 MRI cell tracking using compressed sensing. Magn Reson Med 69:1683–1690

    Article  CAS  PubMed  Google Scholar 

  106. Kampf T, Sturm VJF, Basse-Lusebrink TC et al (2019) Improved compressed sensing reconstruction for [formula: see text]F magnetic resonance imaging. MAGMA 32:63–77

    Article  PubMed  Google Scholar 

  107. Liang S, Dresselaers T, Louchami K, Zhu C, Liu Y, Himmelreich U (2017) Comparison of different compressed sensing algorithms for low SNR (19) F MRI applications-imaging of transplanted pancreatic islets and cells labeled with perfluorocarbons. NMR Biomed 30:e3776

    Article  Google Scholar 

  108. Starke L, Pohlmann A, Prinz C, Niendorf T, Waiczies S (2020) Performance of compressed sensing for fluorine-19 magnetic resonance imaging at low signal-to-noise ratio conditions. Magn Reson Med 84:592–608

    Article  PubMed  Google Scholar 

  109. Chalmers KH, De Luca E, Hogg NH et al (2010) Design principles and theory of paramagnetic fluorine-labelled lanthanide complexes as probes for (19)F magnetic resonance: a proof-of-concept study. Chemistry 16:134–148

    Article  CAS  PubMed  Google Scholar 

  110. Kislukhin AA, Xu H, Adams SR, Narsinh KH, Tsien RY, Ahrens ET (2016) Paramagnetic fluorinated nanoemulsions for sensitive cellular fluorine-19 magnetic resonance imaging. Nat Mater 15:662–668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Jahromi AH, Wang C, Adams SR, Zhu W, Narsinh K, Xu H, Gray DL, Tsien RY, Ahrens ET (2019) Fluorous-soluble metal chelate for sensitive fluorine-19 magnetic resonance imaging nanoemulsion probes. ACS Nano 13:143–151

    Article  CAS  PubMed  Google Scholar 

  112. Wang C, Adams SR, Xu H, Zhu W, Ahrens ET (2019) β-diketonate-iron(III) complex: a versatile fluorine-19 MRI signal enhancement agent. ACS Appl Bio Mater 2:3836–3842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Dan M, Cochran DB, Yokel RA, Dziubla TD (2013) Binding, transcytosis and biodistribution of anti-PECAM-1 iron oxide nanoparticles for brain-targeted delivery. PLoS One 8:e81051

    Article  PubMed  PubMed Central  Google Scholar 

  114. Muro S, Dziubla T, Qiu W, Leferovich J, Cui X, Berk E, Muzykantov VR (2006) Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1. J Pharmacol Exp Ther 317:1161–1169

    Article  CAS  PubMed  Google Scholar 

  115. Shuvaev VV, Ilies MA, Simone E, Zaitsev S, Kim Y, Cai S, Mahmud A, Dziubla T, Muro S, Discher DE, Muzykantov VR (2011) Endothelial targeting of antibody-decorated polymeric filomicelles. ACS Nano 5:6991–6999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Hingorani DV, Chapelin F, Stares E, Adams SR, Okada H, Ahrens ET (2020) Cell penetrating peptide functionalized perfluorocarbon nanoemulsions for targeted cell labeling and enhanced fluorine-19 MRI detection. Magn Reson Med 83:974–987

    Article  CAS  PubMed  Google Scholar 

  117. Christian NA, Milone MC, Ranka SS, Li G, Frail PR, Davis KP, Bates FS, Therien MJ, Ghoroghchian PP, June CH, Hammer DA (2007) Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling. Bioconjug Chem 18:31–40

    Article  CAS  PubMed  Google Scholar 

  118. Temme S, Baran P, Bouvain P, Grapentin C, Krämer W, Knebel B, al-Hasani H, Moll JM, Floss D, Schrader J, Schubert R, Flögel U, Scheller J (2018) Synthetic cargo internalization receptor system for nanoparticle tracking of individual cell populations by fluorine magnetic resonance imaging. ACS Nano 12:11178–11192

    Article  CAS  PubMed  Google Scholar 

  119. Chapelin F, Capitini CM, Ahrens ET (2018) Fluorine-19 MRI for detection and quantification of immune cell therapy for cancer. J Immunother Cancer 6:105

    Article  PubMed  PubMed Central  Google Scholar 

  120. FDA guidance for industry: preclinical assessment of investigational cellular and gene therapy products. https://www.fda.gov/media/87564/download. Accessed 27 Aug 2021

  121. FDA regulatory considerations for human cells, tissues, and cellular and tissue-based products: minimal manipulation and homologous use. https://www.fda.gov/media/109176/download. Accessed 27 Aug 2021

  122. Kaneda MM, Caruthers S, Lanza GM, Wickline SA (2009) Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics. Ann Biomed Eng 37:1922–1933

    Article  PubMed  PubMed Central  Google Scholar 

  123. Ahrens ET, Helfer BM, O'Hanlon CF, Schirda C (2014) Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI. Magn Reson Med 72:1696–1701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Rose LC, Kadayakkara DK, Wang G, Bar-Shir A, Helfer BM, O'Hanlon CF, Kraitchman DL, Rodriguez RL, Bulte JWM (2015) Fluorine-19 labeling of stromal vascular fraction cells for clinical imaging applications. Stem Cells Transl Med 4:1472–1481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR001998, the American Cancer Society Grant IRG-19-140-31 and by the University of Kentucky Lucille P. Markey Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Correspondence to Fanny Chapelin.

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Dr. Chapelin reports grants from NIH, grants from ACS, during the conduct of the study. Dr. Gedaly, Zachary Sweeney and Liza Gossett have nothing to disclose.

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Chapelin, F., Gedaly, R., Sweeney, Z. et al. Prognostic Value of Fluorine-19 MRI Oximetry Monitoring in cancer. Mol Imaging Biol 24, 208–219 (2022). https://doi.org/10.1007/s11307-021-01648-3

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  • DOI: https://doi.org/10.1007/s11307-021-01648-3

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