Fully automated and simplified radiosynthesis of [18F]-3′-deoxy-3′-fluorothymidine using anhydro precursor and single neutral alumina column purification

  • S. K. Nandy
  • M. G. R. Rajan


[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.


[18F]FLT Anhydro precursor DMTThy Neutral-alumina column purification 



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.


  1. 1.
    Barthel H, Perumal M, Latigo J, He Q, Bardy F, Luthara SK, Pierec PM (2005) Eur J Nucl Med Mol Imaging 32:257CrossRefGoogle Scholar
  2. 2.
    Been LB, Suurmeijer AJH, Cobben DCP, Jager PL, Hoekstra HJ, Elsinga PH (2004) Eur J Nucl Med Mol Imaging 31:1659CrossRefGoogle Scholar
  3. 3.
    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 62:3331Google Scholar
  4. 4.
    Chen W, Cloughesy T, Kamadar N, Satyamurthy N, Bergoneider M, Liau L, Mischel P, Czernin J, Phelps ME, Silverman DHS (2005) J Nucl Med 46:945Google Scholar
  5. 5.
    Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-crews JM, Obradovich JE, Muzik O, Mangner TJ (1998) Nat Med 4:1334CrossRefGoogle Scholar
  6. 6.
    Shields AF, Lim K, Grierson J, Link K, Krohn KA (1990) J Nucl Med 31:337Google Scholar
  7. 7.
    Wilson IK, Chatterjee S, Wolf W (1991) J Fluor Chem 55:283CrossRefGoogle Scholar
  8. 8.
    Grierson JR, Shields AF (2000) Nucl Med Biol 27:143CrossRefGoogle Scholar
  9. 9.
    Wodarski C, Eisenbarth J, Naber K, Henze M, Haberkorn U, Eisenhut M (2000) J Labelled Comp Radiopharm 43:1211–1218CrossRefGoogle Scholar
  10. 10.
    Martin SJ, Eisenbarth JA, Wagner-Utermann U, Mier W, Henze M, Prizkow H, Haberkorn U, Eisenhut M (2002) Nucl Med Biol 29:263–273CrossRefGoogle Scholar
  11. 11.
    Machulla HJ, Blocher A, Kuntzsch M, Piert M, Wei R, Grierson JR (2000) J Radioanal Nucl Chem 243:843CrossRefGoogle Scholar
  12. 12.
    Blocher A, Kunzsch R, Wei R, Machulla HJ (2002) J Radioanal Nucl Chem 251:55CrossRefGoogle Scholar
  13. 13.
    Windhorst AD, Klein PJ, Eisenbarth J, Oeser T, Kruijer PS, Eisenhut M (2008) Nucl Med Biol 35:413CrossRefGoogle Scholar
  14. 14.
    Nandy SK, Rajan MGR, Korde A, Chaudhari PR (2007) J Labelled Comp Radiopharm 50:S121Google Scholar
  15. 15.
    Nandy SK, Krishnamurthy NV, Rajan MGR (2009) J Radioanal Nucl Chem. doi: 10.1007/s10967-0322-1
  16. 16.
    Tewson TJ, Paulsen A, El-Shafie F (2003) J Labelled Comp Radiopharm 46:S222Google Scholar
  17. 17.
    Nakao R, Kida T, Suzuki B (2005) Appl Radiat Isot 62:889CrossRefGoogle Scholar
  18. 18.
    Demirtas I, Buyukkidin S, Elmastas M (2002) Turk J Chem 26:889Google Scholar
  19. 19. (Product CAS Number: 67-68-5)
  20. 20.
    Choi MF, Hawkins P (1995) Spectrochim Acta 51A:579Google Scholar
  21. 21.
    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)Google Scholar
  22. 22.
    Salskov A, Tammisetli S, Grierson J, Vesselle H (2007) Semin Nucl Med 37:429CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2009

Authors and Affiliations

  1. 1.Radiation Medicine Centre, Bio-Medical GroupBhabha Atomic Research Centre, Tata Memorial Hospital AnnexeMumbaiIndia

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