To use 19F imaging tracer (19FIT-27) to evaluate kinetics in major organs.
Kinetics studies using proton MRI are difficult because of low concentration of 19FIT-27 protons relative to background water protons. Because there is no background source of 19F NMR in a biological body, 19F may be an ideal nucleus to directly trace 19FIT-27. However, there are several challenges for reliable 19F MR imaging and spectroscopy, particularly with clinical whole-body MRI systems, which include low concentrations and long 19F T1.
Methods and materials
We performed a dynamic 19F MRI study on mice at a 3T whole-body MRI system using a homemade transmit/receive (Tx/Rx) switch and a Tx/Rx volume RF coil. We used a newly developed fluorine imaging agent, which has 27 identical fluorine atoms with identical chemical shift, a relatively short T1, and high hydrophilicity. Basic kinetics parameters were estimated from the 19F signal-time curve.
Results and discussions
Resultant fluorine images show fairly high spatial (3 × 3 × 3 mm3) and temporal resolutions. Biodistribution and kinetics of 19FIT-27 are obtained via 19F images for major uptake organs.
Whole-body dynamic 19F MRI of newly developed 19FIT-27 in mice was obtained with fairly high spatial and temporal resolutions on a 3T clinical MRI system. The present study demonstrates the feasibility of 19F MRI using our newly developed compound to investigate major organ kinetics.
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Reid DG, Murphy PS (2008) Fluorine magnetic resonance in vivo: a powerful tool in the study of drug distribution and metabolism. Drug Discov Today 13(11–12):473–480
Kim SH, Csaky KG, Wang NS, Lutz RJ (2008) Drug elimination kinetics following subconjunctival injection using dynamic contrast-enhanced magnetic resonance imaging. Pharm Res 25(3):512–520
Wang Y, Ye F, Jeong EK, Sun Y, Parker DL, Lu ZR (2007) Noninvasive visualization of pharmacokinetics, biodistribution and tumor targeting of poly [N-(2-hydroxypropyl) methacrylamide] in mice using contrast enhanced MRI. Pharm Res 24(6):1208–1212
Leawoods JC, Yablonskiy DA, Saam B, Gierada DS, Conradi MS (2001) Hyperpolarized He-3 gas production and MR imaging of the lung. Concepts Magn Reson 13:277–293
Klomp D, Van Laarhoven H, Scheenen T, Kamm Y, Heerschap A (2007) Quantitative 19F MR spectroscopy at 3T to detect heterogeneous capecitabine metabolism in human liver. NMR Biomed 20(5):485–492
Schneider E, Bolo NR, Frederick B, Wilkinson S, Hirashima F, Nassar L, Lyoo IK, Koch P, Jones S, Hwang J, Sung Y, Villafuerte RA, Maier G, Hsu R, Hashoian R, Renshaw PF (2006) Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole. J Clin Pharm Ther 31(3):261–273
Van Laarhoven HWM, Punt CJA, Kamm YJL, Heerschap A (2005) Monitoring fluoropyrimidine metabolism in solid tumors with in vivo 19F magnetic resonance spectroscopy. Crit Rev Oncol Hematol 56(3):321–343
Porcari P, Capuani S, D’Amore E, Lecce M, La Bella A, Fasano F, Migneco LM, Campanella R, Maraviglia B, Pastore FS (2009) In vivo 19F MR imaging and spectroscopy for the BNCT optimization. Appl Radiat Isot 67(7 Sup):S365–S368
Procissi D, Claus F, Burgman P, Koziorowski J, Chapman JD, Thakur SB, Matei C, Ling CC, Koutcher JA (2007) In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors. Clin Cancer Res 13(12):3738–3747
Ramaprasad S (2005) In vivo magnetic resonance measures of dark cytotoxicity of photosensitizers in a murine tumor model. Proc SPIE. https://doi.org/10.1117/12.593798
van Zijl PC, Ligeti L, Sinnwell T, Alger JR, Chesnick AS, Moonen CT, McLaughlin AC (1990) Measurement of cerebral blood flow by volume-selective 19F NMR spectroscopy. Magn Reson Med 16(3):489–495
Janjic JM, Ahrens ET (2009) Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(5):492–501
Liu X, Li SK, Jeong EK (2010) Ocular pharmacokinetic study of a corticosteroid by 19F MR. Exp Eye Res 91:347–352
Bartels M, Albert K (1995) Detection of psychoactive drugs using 19F MR spectroscopy. J Neural Transm Gen Sect 99(1–3):1–6
Kamm YJL, Heerschap A, van den Bergh EJ, Wagener DJT (2004) 19F-magnetic resonance spectroscopy in patients with liver metastases of colorectal cancer treated with 5-fluorouracil. Anticancer Drugs 15(3):229–233
Dresselaers T, Theys J, Nuyts S, Wouters B, De Bruijn E, Anné J, Lambin P, Van Hecke P, Landuyt W (2003) Non-invasive 19F MR spectroscopy of 5-fluorocytosine to 5-fluorouracil conversion by recombinant Salmonella in tumours. Br J Cancer 89(9):1796–1801
Kimura A, Narazaki M, Kanazawa Y, Fujiwara H (2004) 19F magnetic resonance imaging of perfluorooctanoic acid encapsulated in liposome for biodistribution measurement. Magn Reson Imaging 22(6):855–860
Bolo NR, Hodé Y, Nédélec JF, Lainé E, Wagner G, MacHer JP (2000) Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. Neuropsychopharmacology 23(4):428–438
Doi Y, Shimmura T, Kuribayashi H, Tanaka Y, Kanazawa Y (2009) Quantitative 19F imaging of nmol-level F-nucleotides/-sides from 5-FU with T2 mapping in mice at 9.4T. Magn Reson Med 62(5):1129–1139
Brix G, Schlicker A, Mier W, Peschke P, Bellemann ME (2005) Biodistribution and pharmacokinetics of the F-19-labeled radiosensitizer 3-aminobenzamide: assessment by 19F MR imaging. Magn Reson Imaging 23(4):428–438
Jiangs ZX, Yu YB (2010) Fluorous mixture synthesis of asymmetric dendrimers. J Org Chem 75(6):2044–2049
Jiang ZX, Liu X, Jeong EK, Yu YB (2009) Symmetry-guided design and fluorous synthesis of a stable and rapidly excreted imaging tracer for 19F MRI. Angew Chem Int Ed 48(26):4755–4768
Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET (2007) Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med 58(4):725–734
Chalmers KH, De Luca E, Hogg NHM, Kenwright AM, Kuprov I, Parker D, Botta M, Ian Wilson J, Blamire AM (2010) Design principles and theory of paramagnetic fluorine-labelled lanthanide complexes as probes for 19F magnetic resonance: a proof-of-concept study. Chem A Eur J 16(1):134–148
Neubauer AM, Myerson J, Caruthers SD, Hockett FD, Winter PM, Chen J, Gaffney PJ, Robertson JD, Lanza GM, Wickline SA (2008) Gadolinium-modulated 19F signals from perfluorocarbon nanoparticles as a new strategy for molecular imaging. Magn Reson Med 60(5):1066–1072
Jiang ZX, Feng Y, Yu YB (2011) Fluorinated paramagnetic chelates as potential multi-chromic 19F tracer agents. Chem Commun 47(25):7233–7235
This work was supported by NSF CBET 1133908.
Conflict of interest
All authors declare that they have no conflict of interest.
The study did not involve any human subject, therefore no ethical standard is required.
No informed consent is required.
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Liu, X., Jiang, Z., Yu, B.Y. et al. Study of kinetics of 19F-MRI using a fluorinated imaging agent (19FIT) on a 3T clinical MRI system. Magn Reson Mater Phy 32, 97–103 (2019). https://doi.org/10.1007/s10334-018-0707-7
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