Abstract
[18F]-3′-deoxy-3′-fluorothymidine ([18F]FLT) is an established positron emission tomograph (PET)—radiopharmaceutical to study cell-proliferation rate in tumors. Very low practical yield, uncertain and time-consuming high performance liquid chromatography (HPLC) purification, are the main obstacles for the routine use of [18F]FLT in clinical PET. To obviate these difficulties, we have developed a fully automated radiosynthesis procedure for [18F]FLT using 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydro-thymidine (DMTThy) and simplified single neutral alumina column purification. The [18F]FLT yield was 8.48 ± 0.93% (n = 5) (without radioactive decay correction) in a synthesis time of 68 ± 3 min. The radiochemical purity was greater than 95% as confirmed by analytical HPLC using reference standard FLT and also free of non-radioactive impurity. Soluble aluminum in the final product was much below the permissible limits. Di-methyl sulfoxide (DMSO), the reaction medium, could be detected in the final product in trace amounts, well below the permissible levels. The synthesized [18F]FLT was sterile and bacterial endotoxin free by appropriate tests. PET imaging study in normal rabbits showed distinct localization of [18F]FLT in organs having rapid cell division rate like bone marrow, guts and snout and the excretion was through the renal route. There were no significant uptakes in bone and brain. The former finding confirms the in vivo stability of the [18F]FLT. This simplified radiosynthesis procedure can easily be adapted in any commercial or indigenous [18F]FDG synthesis module for routine [18F]FLT synthesis without the need of additional automation for HPLC purification.
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Barthel H, Perumal M, Latigo J, He Q, Bardy F, Luthara SK, Pierec PM (2005) Eur J Nucl Med Mol Imaging 32:257
Been LB, Suurmeijer AJH, Cobben DCP, Jager PL, Hoekstra HJ, Elsinga PH (2004) Eur J Nucl Med Mol Imaging 31:1659
Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Gatting G, Mattfeldt T, Liewald F, Reske SN, Neumaier B (2002) Cancer Res 62:3331
Chen W, Cloughesy T, Kamadar N, Satyamurthy N, Bergoneider M, Liau L, Mischel P, Czernin J, Phelps ME, Silverman DHS (2005) J Nucl Med 46:945
Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-crews JM, Obradovich JE, Muzik O, Mangner TJ (1998) Nat Med 4:1334
Shields AF, Lim K, Grierson J, Link K, Krohn KA (1990) J Nucl Med 31:337
Wilson IK, Chatterjee S, Wolf W (1991) J Fluor Chem 55:283
Grierson JR, Shields AF (2000) Nucl Med Biol 27:143
Wodarski C, Eisenbarth J, Naber K, Henze M, Haberkorn U, Eisenhut M (2000) J Labelled Comp Radiopharm 43:1211–1218
Martin SJ, Eisenbarth JA, Wagner-Utermann U, Mier W, Henze M, Prizkow H, Haberkorn U, Eisenhut M (2002) Nucl Med Biol 29:263–273
Machulla HJ, Blocher A, Kuntzsch M, Piert M, Wei R, Grierson JR (2000) J Radioanal Nucl Chem 243:843
Blocher A, Kunzsch R, Wei R, Machulla HJ (2002) J Radioanal Nucl Chem 251:55
Windhorst AD, Klein PJ, Eisenbarth J, Oeser T, Kruijer PS, Eisenhut M (2008) Nucl Med Biol 35:413
Nandy SK, Rajan MGR, Korde A, Chaudhari PR (2007) J Labelled Comp Radiopharm 50:S121
Nandy SK, Krishnamurthy NV, Rajan MGR (2009) J Radioanal Nucl Chem. doi:10.1007/s10967-0322-1
Tewson TJ, Paulsen A, El-Shafie F (2003) J Labelled Comp Radiopharm 46:S222
Nakao R, Kida T, Suzuki B (2005) Appl Radiat Isot 62:889
Demirtas I, Buyukkidin S, Elmastas M (2002) Turk J Chem 26:889
www.sigmaaldrich.com/catalogue (Product CAS Number: 67-68-5)
Choi MF, Hawkins P (1995) Spectrochim Acta 51A:579
Impurities: residual solvents in new veterinary medicinal products, active substances and excipients, VICH Topic GL18 (Impurities Solvents), June 2000 (Recommended for Implementation at Step 7 of the VICH Process)
Salskov A, Tammisetli S, Grierson J, Vesselle H (2007) Semin Nucl Med 37:429
Acknowledgements
Thanks to Mr. B. P. Tiwari, Radiation Medicine Centre, Bhabha Atomic Research Centre (BARC) for helping in PET imaging studies. Special thanks to Mr. Arpit Mitra, Medical Cyclotron Facility, Board of Radiation and Isotope Technology (BRIT), for analyzing the samples for sterility and BET.
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Nandy, S.K., Rajan, M.G.R. Fully automated and simplified radiosynthesis of [18F]-3′-deoxy-3′-fluorothymidine using anhydro precursor and single neutral alumina column purification. J Radioanal Nucl Chem 283, 741–748 (2010). https://doi.org/10.1007/s10967-009-0429-4
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DOI: https://doi.org/10.1007/s10967-009-0429-4