Nuclear Medicine and Biology
Volume 34, Issue 3 , Pages 283-291 , April 2007

Synthesis and evaluation of a 99mTc-MAMA-propyl-thymidine complex as a potential probe for in vivo visualization of tumor cell proliferation with SPECT

  • Sofie Celen

      Affiliations

    • Laboratory for Radiopharmacy, K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Tjibbe de Groot

      Affiliations

    • Radiopharmacy, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Jan Balzarini

      Affiliations

    • Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Kathleen Vunckx

      Affiliations

    • Nuclear Medicine, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Christelle Terwinghe

      Affiliations

    • Radiopharmacy, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Peter Vermaelen

      Affiliations

    • Nuclear Medicine, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Lizette Van Berckelaer

      Affiliations

    • Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Hubert Vanbilloen

      Affiliations

    • Radiopharmacy, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Johan Nuyts

      Affiliations

    • Nuclear Medicine, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Luc Mortelmans

      Affiliations

    • Nuclear Medicine, U.Z. Gasthuisberg K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Alfons Verbruggen

      Affiliations

    • Laboratory for Radiopharmacy, K.U. Leuven, B-3000 Leuven, Belgium
    • ,
  • Guy Bormans

      Affiliations

    • Laboratory for Radiopharmacy, K.U. Leuven, B-3000 Leuven, Belgium
    • Corresponding Author InformationCorresponding author. Laboratorium for Radiopharmacy, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium. Tel.: +32 16 330447; fax: +32 16 330449.

Received 19 November 2006 ,Revised 18 December 2006 ,Accepted 5 January 2007.

References 

  1. Kenny LM, Aboagye EO, Price PM. Positron emission tomography imaging of cell proliferation in oncology. Clin Oncol. 2004;16:176–185
  2. Shields AF, Grierson JR, Dohmen BM, Machulla H-J, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998;4:1334–1336
  3. Herholz K, Rudolf J, Heiss WD. FDG transport and phosphorylation in human gliomas measured with dynamic PET. J Neurooncol. 1992;12:159–165
  4. Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med. 1992;33:1972–1980
  5. Vander Borght T, Labar D, Pauwels S, Lambotte L. Production of [2-11C]thymidine for quantification of cellular proliferation with PET. Appl Radiat Isot. 1991;42:103–104
  6. Lu L, Samuelsson L, Bergström M, Sato K, Fasth K-J, Langström B. Rat studies comparing 11C-FMAU, 18F-FLT and 76Br-BFU as proliferation markers. J Nucl Med. 2002;43:1688–1698
  7. Shields AF. PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med. 2003;44:1432–1433
  8. Barthel H, Perumal M, Latigo J, He Q, Brady F, Luthra SK, et al. The uptake of 3′-deoxy-3′-[18F]fluorothymidine into L5178Y tumours in vivo is dependent on thymidine kinase 1 protein levels. Eur J Nucl Med Mol Imaging. 2005;32:257–263
  9. Shields AF, Grierson JR, Kozawa SM, Zheng M. Development of labeled thymidine analogs for imaging tumor proliferation. Nucl Med Biol. 1996;23:17–22
  10. Conti PS, Alauddin MM, Fissekis JR, Schmall B, Watanabe KA. 2′-Fluoro-5-[11C]-methyl-β-d-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET. Nucl Med Biol. 1995;22:783–789
  11. Arnér ESJ, Eriksson S. Mammalian deoxyribonucleoside kinases. Pharmacol Ther. 1995;67:155–186
  12. Welin M, Kosinska U, Mikkelsen NE, Carnrot C, Zhu C, Wang L, et al. Structures of thymidine kinase 1 of human and myoplasmic origin. Proc Natl Acad Sci U S A. 2004;101:17970–17975
  13. Hengstschläger M, Knöflers M, Müllner EW, Ogris E, Wintersberger E, Wawra E. Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells. J Biol Chem. 1994;269:13836–13842
  14. Johansson NG, Eriksson S. Structure–activity relationships for phosphorylation of nucleoside analogs to monophosphates by nucleoside kinases. Acta Biochim Pol. 1996;43:143–160
  15. Lunato AJ, Wang J, Woollard JE, Anisuzzaman AKM, Ji W, Rong F-G, et al. Synthesis of 5-(carboranylalkylmercapto)-2′-deoxyuridines and 3-(carboranalkyl)thymidine and their evaluation as substrates for human thymidine kinases 1 and 2. J Med Chem. 1999;42:3378–3389
  16. Al-Madhoun AS, Johnsamuel J, Yan J, Ji W, Wang J, Zhuo J-C, et al. Synthesis of a small library of 3-(carboranylalkyl)thymidines and their biological evaluation as substrates for human thymidine kinases 1 and 2. J Med Chem. 2002;45:4018–4028
  17. Al-Madhoun AS, Johnsamuel J, Barth RF, Tjarks W, Eriksson S. Evaluation of human thymidine kinase 1 substrates as new candidates for boron neutron capture therapy. Cancer Res. 2004;64:6280–6286
  18. Byun Y, Thirumamagal BTS, Yang W, Eriksson S, Barth RF, Tjarks W. Preparation and biological evaluation of 10B-enriched 3-[5-(2-(2,3-dihydroxyprop-1-yl)-o-carboran-1-yl(pentan-1-yl]thymidine (N5-2OH), a new boron delivery agent for boron neutron capture therapy of brain tumors. J Med Chem. 2006;49:5513–5523
  19. Bandyopadhyaya AK, Johnsamuel J, Al-Madhoun AS, Eriksson S, Tjarks W. Comparative molecular field analysis and comparative molecular similarity indices analysis of human thymidine kinase 1 substrates. Bioorgan Med Chem. 2005;13:1681–1689
  20. Sampson CB. Textbook of radiopharmacy. Theory and practice. 3rd ed.. The Netherlands: Gordon and Breach Science Publishers; 1999;
  21. Neill OJP, Wilson SR, Katzenellebogen JA. Preparation and structural characterization of monoamine–monoamide bis(thiol) oxo complexes of Technetium(V) and Rhenium(V). Inorg Chem. 1994;33:319–323
  22. Yamauchi H, Takahashi J, Seri S, Kawashima H, Koike H, Kato-Azuma M. In vitro and in vivo characterization of a new series of Tc-99m complexes with N2S2 ligands. In:  Nicolini M,  Bandoli G,  Mazzi U editor. Technetium and rhenium in chemistry and nuclear medicine 3. Verona (Italy): Cortina International; 1989;p. 475–502
  23. Vanbilloen HP, Kieffer D, Cleynhens J, Bormans G, Mortelmans L, Verbruggen AM. Development and biological evaluation of 99mTc-BAT-tropane esters. Nucl Med Biol. 2005;32:607–612
  24. Balzarini J, Celen S, Karlsson A, de Groot T, Verbruggen A, Bormans G. The effect of a methyl or 2-fluoroethyl substituent at N-3 position of thymidine, 3′-fluoro-3′-deoxythymidine and 1-β-d-arabinofuranosylthymine on their antiviral and cytostatic activity in cell culture. AVCC. 2006;17:17–23
  25. Loening A, Crump Institute for Molecular Imaging , UCLA School of Medicine, California, USA . http://sourceforge.net/projects/amide/
  26. Oya S, Plössl K, Kung MP, Stevenson A, Kung HF. Small and neutral Tv(V)O BAT bisaminothiol (N2S2) complexes for developing new brain imaging agents. Nucl Med Biol. 1998;25:135–140
  27. Schmid M, Neumaier B, Vogg ATJ, Wczasek K, Friesen C, Mottaghy FM, et al. Synthesis and evaluation of a radiometal-labeled macrocyclic chelator-derivatised thymidine analog. Nucl Med Biol. 2006;33:359–366
  28. Levin VA. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem. 1980;23:682–684
  29. Young RC, Mitchell RC, Brown TH, Ganellin CR, Griffiths R, Jones M, et al. Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists. J Med Chem. 1988;31:656–671

PII: S0969-8051(07)00010-8

doi: 10.1016/j.nucmedbio.2007.01.003

Nuclear Medicine and Biology
Volume 34, Issue 3 , Pages 283-291 , April 2007

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