19F MRI As a tool for imaging drug delivery to tissue and individual cells
DOI:
https://doi.org/10.15584/ejcem.2017.2.3Keywords:
drug delivery, drug tracking, fluorine, magnetic resonance imagingAbstract
Over the past few decades, magnetic resonance imaging (MRI) has proven to be extremely successful in medical applications. More recently, the biomedical applications of MRI have been gaining more use in the field of clinical pharmacy. In 1977, perfluorocarbon compounds (PFC), which form emulsions that can carry drugs, were analyzed by 19F MRI and emulsified PFC compounds have been investigated as potential blood substitutes since the early 1960s and now a wide variety of PFC compounds are currently available as 19F MRI biomarkers. Molecules with 19F substituents are particularly attractive for use in drug tracking by 19F MRI due to 100% 19F abundance, high 19F MRI sensitivity (0.83 relative to 1H MRI) and an impressively large chemical shift range (400 ppm). Another benefit in the use of 19F MRI is a zero background signal in biological samples due to lack of endogenous fluorine. Therefore, drugs containing fluorine atom have potential for 19F MRI imaging drug delivery to tissue. This article will review recent developments in the use of 19F MRI in imaging drug delivery to tissue and individual cells.Downloads
References
Hagmann WK. The many roles for fluorine in medicinal chemistry. J Med Chem. 2008; 51:4359-69.
Heidelberger C, Chaudhuri NK, Daneberg P, Mooren D, Griesbach L, Duschinsky R. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 1957;179:663-66.
Holland GN, Bottomley PA, Hinshaw WS. 19F magnetic resonance imaging. J Mag Res. 1977;28(1):133-136.
Janjic JM, Ahrens ET. Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscipl Rev Nanomed Nanobiotech. 2005;1(5):492-01.
Ahrens ET, Flores R, Xu H, Morel PA. In vivo imaging platform for tracking immunotherapeutic cells. Nature Biotechnol. 2005;23(8):983-87.
Ruiz-Cabello J, Barnett BP, Bottomley PA, Bulte JWM. Fluorine 19F MRS and MRI in biomedicine. NMR in Biomed. 2011;24(2):114-29.
Kamm YJL, Heerschap A, van den Bergh EJ, Wagener DJT. 19F-magnetic resonance spectroscopy in patients with liver metastases of colorectal cancer treated with 5-fluorouracil. Anti-Cancer Drugs. 2004;15(3):229-33.
Wang X, Chen J, Wang D, Dong S, Hao J, Hoffmann H. Monitoring the different micelle species and the slow kinetics of tetraethylammonium perfluorooctane-sulfonate by 19F NMR spectroscopy. Advances in Colloid and Interface Science. 2017; DOI:10.1016/j.cis.2017.05.016
Drouza C, Dieronitou A, Hadjiadamou I, Stylianou M. Investigation of phenols activity in early stage oxidation of edible oils by electron paramagnetic resonance and 19F NMR spectroscopies using novel lipid vanadium complexes as radical initiators. J Agric Food Chem. 2017;65(24):4942-4951.
Hu H, Katyayan KK, Czeskis BA, Perkins EJ, Kulanthaivel P. Comparison between radioanalysis and 19F Nuclear Magnetic Resonance Spectroscopy in the determination of mass balance, metabolism, and distribution of pefloxacin. Drug Metab Dispos. 2017;45(4):399-08.
Vints I, Gatenyo J, Rozen S. Fluorination of aryl boronic acids using acetyl hypofluorite made directly from diluted fluorine. J. Org. Chem. 2013;78(23):11794-97.
Gatenyo J, Hagooly Y, Vints I, Rozen S. Activation of a CH bond in polypyridine systems by acetyl hypofluorite made from F2. Organic & Biomol Chem. 2012;10(9):1856/60.
Liu Z, Shibata N, Takeuchi Y. Novel methods for the facile construction of 3,3-disubstituted and 3, 3-spiro-2H,4H-benzo[e]1,2-thiazine-1,1-diones: synthesis of (11S,12R, 14R)-2-fluoro-14-methyl-11-(methylethyl)spiro[4H-benzo[e]- 1, 2-thiazine-3,2'-cyclohexane]-1,1-dione, an agent for the electrophilic asymmetric fluorination of aryl ketone enolates. J Org Chem. 2000;65(22):7583-7.
Vora HU, Rovis T. N-Heterocyclic carbene catalyzed asymmetric hydration: direct synthesis of alpha-protio and alpha-deuterio alpha-chloro and alpha-fluoro carboxylic acids. J Am Chem Soc. 2010;132(9):2860-61.
Bennasar ML, Zulaica E, Juan C, Alonso Y, Bosch J. Addition of ester enolates to N-alkyl-2-fluoropyridinium salts: total synthesis of (+/-)-20-deoxycamptothecin and (+)-camptothecin. J Org Chem. 2002;67(21):7465-74.
Kamm YJ, Heerschap, van den Bergh EJ, Wagener DJ. 19F-magnetic resonance spectroscopy in patients with liver metastases of colorectal cancer treated with 5-fluorouracil. Anticancer Drugs. 2004;15(3):229-33.
Stanosz M, Stanosz S, Puchalski A. An assessment of the influence of fluoride, modified transdermal replacement hormone therapy and supplement hormone therapy on unmanageable osteoporosis in postmenopausal women. J Elementol. 2009;14(3):545–551.
Lucas V, Sicre J, Laredo JD, Guérin C, Kuntz D, Dryll A. Spontaneous fracture of the femur neck in a female patient with osteoporosis treated with sodium fluoride, Rev Rhum Mal Osteoartic. 1990;5(7-8):545-48.
Zhang Q, Gladden L, Avalle P, Mantle M. In vitro quantitative 1H and 19F nuclear magneticresonance spectroscopy and imaging studies of fluvastatin™ in Lescol® XL tablets in a USP-IV dissolution cell. J Control Release. 2011;156(3):345-54.
White TE, Surles-Zeigler MC, Ford GD, et al. Bilateral gene interaction hierarchy analysis of the cell death gene response emphasizes the significance of cell cycle genes following unilateral traumatic brain injury. BMC Genomics. 2016;17:130.
Stolarczyk M, Apola A, Krzek J, Sajdak A. Validation of derivative spectrophotometry method for determination of active ingredients from neuroleptics in pharmaceutical preparations. Acta Pol Pharm Drug Res. 2009;66(4):351-56.
Bolo NR, Hode Y, Macher JP . Fluorine magnetic resonance spectroscopy measurement of brain fluvoxamine and fluoxetine in pediatric patients treated for pervasive developmental disorders. MAGMA. 2016(6):268-76.
Takeda T, Makita K, Ishikawa S, Kaneda K, Yokoyama K, Amaha K. Uptake and elimination of sevoflurane in rabbit tissues-an in vivo magnetic resonance spectroscopy study. Can J Anaesth. 2000;47(6):579-84.
Pablos AI, Escobar I, Albin˜ana S, Serrano O, Ferrari JM, de Tejada AH. Evaluation of an antibiotic intravenous to oral sequential therapy program. Pharmacoepidemiol drug safety. 2005;14:53–59.
Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psych. 2002;63(9):763-71.
Sijens PE, Mostert JP , Irwan R , Potze JH , Oudkerk M , De Keyser J. Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging. Psychiatry Res. 2008;164(3):274-82.
Vakirlis E, Kastanis A, Ioannides D. Calcipotriol/betamethasone dipropionate in the treatment of psoriasis vulgaris. Ther Clin Risk Manag. 2008;4(1):141–48.
Lim YT, Cho MY, Kang JH, et al. Perfluorodecalin/[InGaP/ZnS quantum dots] nanoemulsions as 19F MR/optical imaging nanoprobes for the labeling of phagocytic and nonphagocytic immune cells. Biomaterials. 2010;31(18):4964-71.
Bartusik D, Tomanek B, Lattová E, Perreault H, Fallone G. Combined treatment of human MCF-7 breast carcinoma with antibody, cationic lipid and hyaluronic acid using ex vivo assays. J Pharm Biomed Anal. 2010;51(1):192-01.
Ahrens ET1, Bulte JW. Tracking immune cells in vivo using magnetic resonance imaging. Nat Rev Immunol. 2013;13(10):755-63.
Managh AJ, Edwards SL, Bushell A, et al. Single cell tracking of gadolinium labeled CD4+ T cells by laser ablation inductively coupled plasma mass spectrometry. Anal Chem. 2013;85(22):10627-34.
Bartels M, Albert K. Detection of psychoactive drugs using 19F MR spectroscopy. J Neural Transm Gen Sect. 1995;99(1-3):1-6.
Chubarova AS, Zakharovaa OD, Kovala OA, et al. Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging. Bioorg Med Chem. 2015;23:6943–54.
Ahrens ET, Helfer BM, O'Hanlon CF, Schirda C. Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine-19 MRI. Magn Reson Med. 2014;72(6):1696-01.
Amiri H, Srinivas M, Veltien A, van Uden MJ, de Vries IJ, Heerschap A. Cell tracking using 19F magnetic resonance imaging: Technical aspects and challenges towards clinical applications. Eur Radiol. 2015;25(3):726-35.
Waters EA, Chen K, Allen JS, Zhang H, Lanza GM, Wickline SA. Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS. J Card Magn Reson. 2008;10:43-45.
Higuchi M, Iwata N, Matsuba Y, Sato K, Sasamoto K, Saido TC. 19F and 1H MRI detection of amyloid beta plaques in vivo. Nat Neurosci. 2005;8(4):527-33.
Tooyama I, Yanagisawa D, Taguchi H, et al. Amyloid imaging using fluorine-19 magnetic resonance imaging 19F MRI. Ageing Res Rev. 2016;30:85-94.
Matei E, Gronenborn AM. 19F Paramagnetic Relaxation Enhancement: A Valuable Tool for Distance Measurements in Proteins. Angew Chem Int Ed Engl. 2016;55(1):150-54.
Neubauer AM, Caruthers SD, Hockett FD, et al. Fluorine cardiovascular magnetic resonance angiography in vivo at 1.5 T with perfluorocarbon nanoparticle contrast agents. J Cardiovasc Magn Reson. 2007;9(3):565-73.
Bartusik D, Tomanek B. Detection of fluorine labeled Herceptin using cellular 19F MRI ex vivo. J Pharm Biomed Anal. 2010;51(4):894-900.
Bartusik D, Tomanek B, Siluk D, Kaliszan R. 19F MRI of 3D CEM cells to study the effects of tocopherols and tocotrienols. J Pharm Biomed Anal. 2010;53(3):599-02.
Nobs L, Buchegger F, Gurny R, Allémann E. Surface modification of poly(lactic acid) nanoparticles by covalent attachment of thiol groups by means of three methods. Int J Pharm. 2003;250(2):327-37.
Bartusik D, Tomanek B, Siluk D, Kaliszan R, Fallone G. The application of 19F magnetic resonance ex vivo imaging of three-dimensional cultured breast cancer cells to study the effect of delta-tocopherol. Anal Biochem. 2009;387(2):315-17.
Clarkson PM. Antioxidants and Physical Performance. Crit Rev Food Sci Nutr. 1995;35:131-41.
Fleischauer AT, Simonsen N, Arab L. Antioxidant supplements and risk of breast cancer recurrence and breast cancer-related mortality among postmenopausal women. Nutr Cancer. 2003;46:15-22.
Meydani M, Evans WJ, Handelman G, et al. Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. Am J Physiol. 1993;264:992-998.
Buttner GR, Burns CP. Vitamin E slows the rate of free radical mediated lipid peroxidation in cells. Arch Biochem Biophys. 1996;334:261-67.
Hunter D A. prospective study of the Intake of Vitamins C, E, and A, and the risk of breast cancer. New Eng J Med. 1993;329:234-40.
Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, Helzlsouer KJ. Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol. 2003;157:335-44.
Schwenke DC. Does lack of tocopherols and tocotrienols put women at increased risk of breast cancer? J Nutr Biochem. 2002;13:2-20.
Galli F, Stabile AM, Betti M, et al. The effect of alpha- and gamma-tocopherol and their carboxyethyl hydroxychroman metabolites on prostate cancer cell proliferation. Arch Biochem Biophys 2004;423:97-02.
Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Canall R, Virgill F. Tocotrienol-Rich Fraction from Palm Oil and Gene Expression in Human Breast Cancer Cells. Ann NY Acad Sci. 2004;1031:143-57.
Kashiwagi K, Harada K, Yano Y, et al. A redox-silent analogue of tocotrienol inhibits hypoxic adaptation of lung cancer cells. Biochem Biophys Res Commun. 2008;365:875-81.
Ditsch N, Mayer B, Rolle M. Estrogen receptor expression profile of disseminated epithelial tumor cells in bone marrow of breast cancer patients, Recent Results. Cancer Res. 2003;162:141-47.
McIntyre BS, Briski KP, Gapor A, Sylvester PW. Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells. Proc Soc Exp Biol Med. 2000;224:292-01.
Vu-Quanga H, Vinding MS, Xia D, et al. Chitosan-coated poly(lactic-co-glycolic acid) perfluorooctyl bromide nanoparticles for cell labeling in 19F magnetic resonance imaging. Carbohydrate Polym. 2016;136:936–44.
Yu M, Xie D, Phan KP, Enriquez JS, Luci JJ, Que ML. A CoII complex for 19F MRI-based detection of reactive oxygen species. Chem Commun. 2016;52:13885-88.
Shi Y, Oeh J, Eastham-Anderson J, et al. Mapping in vivo tumor oxygenation within viable tumor by 19F MRI and multispectral analysis. Neoplasia. 2013;15(11):1241-50.
Giraudeau C, Djemaï B, Ghaly MA, et al. High sensitivity 19F MRI of a perfluorooctyl bromide emulsion: application to a dynamic biodistribution study and oxygen tension mapping in the mouse liver and spleen. NMR Biomed. 2012;25(4):654-60.
Liu S, Shah SJ, Wilmes LJ, et al. Quantitative tissue oxygen measurement in multiple organs using 19F MRI in a rat model. Magn Reson Med. 2011;66(6):1722-30.
Zhong J, Sakaki M, Okada H, Ahrens ET. 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. 2013;8(5):59479-83.
Baete SH, Vandecasteele J, De Deene Y. 19F MRI oximetry: simulation of perfluorocarbon distribution impact. Phys Med Biol. 2011;56(8):2535-57.
Magat J, Jordan BF, Cron GO, Gallez B. Noninvasive mapping of spontaneous fluctuations in tumor oxygenation using 19F MRI. Med Phys. 2010;37(10):5434-41.
Bartusik D, Tomanek B. Application of 19F magnetic resonance to study the efficacy of fluorine labeled drugs in the three-dimensional cultured breast cancer cells. Arch Biochem and Biophys. 2010;(493):234–41.
Komoroski RA, Newton JE, Cardwell D, Sprigg J, Pearce J, Karson CN. In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain. Magn Reson Med. 1994;31(2):204-11.
Waiczies H, Guenther M, Skodowski J, et al. Monitoring dendritic cell migration using 19F/1H magnetic resonance imaging. J Vis Exp. 2013;(73):50251-53.
Peng H, Blakey I, Dargaville B, Rasoul F, Rose S, Whittaker AK. Synthesis and evaluation of partly fluorinated block copolymers as MRI imaging agents. Biomacromolecules. 2009;10(2):374-81.
Code RF, Harrison JE, McNeill KG, Szyjkowski M. In vivo 19F spin relaxation in index finger bones. Magn Reson Med. 1990;13(3):358-69.
Chen J, Pan H, Lanza GM, Wickline SA. Perfluorocarbon nanoparticles for physiological and molecular imaging and therapy. Adv Chronic Kidney Dis. 2013:20(6):466-78.
Winter PM. Perfluorocarbon Nanoparticles: Evolution of a Multimodality and Multifunctional Imaging Agent. Scintifica. 2014; Article ID 746574, 1-10.
Aso Y, Yoshioka S, Miyazaki T, Kawanishi T. Feasibility of 19F NMR for assessing the molecular mobility of flufenamic acid in solid dispersions. Chem Pharm Bull (Tokyo). 2009;57(1):61-4.
Adolphi NL, Kuethe DO. Quantitative mapping of ventilation-perfusion ratios in lungs by 19F MR imaging of T1 of inert fluorinated gases. Magn Reson Med. 2008;59(4):739-46.
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