Advertisement

Study of kinetics of 19F-MRI using a fluorinated imaging agent (19FIT) on a 3T clinical MRI system

  • Xin Liu
  • Zhong-Xing Jiang
  • Bruce Y. Yu
  • Eun-Kee Jeong
Research Article
  • 52 Downloads

Abstract

Purpose

To use 19F imaging tracer (19FIT-27) to evaluate kinetics in major organs.

Introduction

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.

Conclusions

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.

Keywords

19F MRI Kinetics 19FIT 

Notes

Acknowledgements

This work was supported by NSF CBET 1133908.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical standard

The study did not involve any human subject, therefore no ethical standard is required.

Informed Consent

No informed consent is required.

References

  1. 1.
    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):473–480CrossRefGoogle Scholar
  2. 2.
    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):512–520CrossRefGoogle Scholar
  3. 3.
    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):1208–1212CrossRefGoogle Scholar
  4. 4.
    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 13:277–293CrossRefGoogle Scholar
  5. 5.
    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):485–492CrossRefGoogle Scholar
  6. 6.
    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):261–273CrossRefGoogle Scholar
  7. 7.
    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):321–343CrossRefGoogle Scholar
  8. 8.
    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–S368CrossRefGoogle Scholar
  9. 9.
    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):3738–3747CrossRefGoogle Scholar
  10. 10.
    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 CrossRefGoogle Scholar
  11. 11.
    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):489–495CrossRefGoogle Scholar
  12. 12.
    Janjic JM, Ahrens ET (2009) Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(5):492–501CrossRefGoogle Scholar
  13. 13.
    Liu X, Li SK, Jeong EK (2010) Ocular pharmacokinetic study of a corticosteroid by 19F MR. Exp Eye Res 91:347–352CrossRefGoogle Scholar
  14. 14.
    Bartels M, Albert K (1995) Detection of psychoactive drugs using 19F MR spectroscopy. J Neural Transm Gen Sect 99(1–3):1–6CrossRefGoogle Scholar
  15. 15.
    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):229–233CrossRefGoogle Scholar
  16. 16.
    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):1796–1801CrossRefGoogle Scholar
  17. 17.
    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):855–860CrossRefGoogle Scholar
  18. 18.
    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):428–438CrossRefGoogle Scholar
  19. 19.
    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):1129–1139CrossRefGoogle Scholar
  20. 20.
    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):428–438Google Scholar
  21. 21.
    Jiangs ZX, Yu YB (2010) Fluorous mixture synthesis of asymmetric dendrimers. J Org Chem 75(6):2044–2049CrossRefGoogle Scholar
  22. 22.
    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):4755–4768CrossRefGoogle Scholar
  23. 23.
    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):725–734CrossRefGoogle Scholar
  24. 24.
    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):134–148CrossRefGoogle Scholar
  25. 25.
    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):1066–1072CrossRefGoogle Scholar
  26. 26.
    Jiang ZX, Feng Y, Yu YB (2011) Fluorinated paramagnetic chelates as potential multi-chromic 19F tracer agents. Chem Commun 47(25):7233–7235CrossRefGoogle Scholar

Copyright information

© European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2018

Authors and Affiliations

  1. 1.Utah Center for Advanced Imaging ResearchUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Radiology and Imaging SciencesUniversity of UtahSalt Lake CityUSA
  3. 3.Wuhan University School of Pharmaceutical SciencesWuhanPeople’s Republic of China
  4. 4.Department of Pharmaceutical SciencesUniversity of MarylandBaltimoreUSA

Personalised recommendations