Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 29-38 , January 2009

5-[18F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

  • Ann-Marie Chacko

      Affiliations

    • Institute for Environmental Medicine, Targeted Therapeutics Program, University of Pennsylvania, Philadelphia, PA 19104, USA
  • ,
  • Eric Blankemeyer

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
  • ,
  • Brian P. Lieberman

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
  • ,
  • Wenchao Qu

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
  • ,
  • Hank F. Kung

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • Corresponding Author InformationCorresponding author. Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3096; fax: +1 215 349 5035.

Received 25 September 2008 ,Accepted 10 October 2008.

References 

  1. Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L, et al. Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet. 2001;358:727–729
  2. Jacobs AH, Rueger MA, Winkeler A, Li H, Vollmar S, Waerzeggers Y, et al. Imaging-guided gene therapy of experimental gliomas. Cancer Res. 2007;67:1706–1715
  3. Lu Y, Dang H, Middleton B, Campbell-Thompson M, Atkinson MA, Gambhir SS, et al. Long-term monitoring of transplanted islets using positron emission tomography. Mol Ther. 2006;14:851–856
  4. Brader P, Riedl CC, Woo Y, Ponomarev V, Zanzonico P, Wen B, et al. Imaging of hypoxia-driven gene expression in an orthotopic liver tumor model. Mol Cancer Ther. 2007;6:2900–2908
  5. Doubrovin M, Ponomarev V, Beresten T, Balatoni J, Bornmann W, Finn R, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA. 2001;98:9300–9305
  6. Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, et al. Imaging the expression of transfected genes in vivo. Cancer Res. 1995;55:6126–6132
  7. Tjuvajev JG, Finn R, Watanabe K, Joshi R, Oku T, Kennedy J, et al. Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res. 1996;56:4087–4095
  8. Alauddin MM, Conti PS. Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET. Nucl Med Biol. 1998;25:175–180
  9. Yaghoubi SS, Couto MA, Chen CC, Polavaram L, Cui G, Sen L, et al. Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. J Nucl Med. 2006;47:706–715
  10. Brust P, Haubner R, Friedrich A, Scheunemann M, Anton M, Koufaki ON, et al. Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression. Eur J Nucl Med. 2001;28:721–729
  11. Alauddin MM, Conti PS, Mazza SM, Hamzeh FM, Lever JR. 9-[(3-[18F]-Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG): a potential imaging agent of viral infection and gene therapy using PET. Nucl Med Biol. 1996;23:787–792
  12. Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, et al. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proc Natl Acad Sci USA. 2000;97:2785–2790
  13. Buursma AR, Rutgers V, Hospers GA, Mulder NH, Vaalburg W, de Vries EF. 18F-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression: in-vitro comparison with other PET tracers. Nucl Med Commun. 2006;27:25–30
  14. Serganova I, Doubrovin M, Vider J, Ponomarev V, Soghomonyan S, Beresten T, et al. Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. Cancer Res. 2004;64:6101–6108
  15. Alauddin MM, Shahinian A, Park R, Tohme M, Fissekis JD, Conti PS. In vivo evaluation of 2′-deoxy-2′-[18F]fluoro-5-iodo-1-beta-d-arabinofuranosyluracil ([18F]FIAU) and 2′-deoxy-2′-[18F]fluoro-5-ethyl-1-beta-d-arabinofuranosyluracil ([18F]FEAU) as markers for suicide gene expression. Eur J Nucl Med Mol Imaging. 2007;34:822–829
  16. Miyagawa T, Gogiberidze G, Serganova I, Cai S, Balatoni JA, Thaler HT, et al. Imaging of HSV-tk reporter gene expression: comparison between [18F]FEAU, [18F]FFEAU, and other imaging probes. J Nucl Med. 2008;49:637–648
  17. Chin FT, Namavari M, Levi J, Subbarayan M, Ray P, Chen X, et al. Semiautomated radiosynthesis and biological evaluation of [18F]FEAU: a novel PET imaging agent for HSV1-tk/sr39tk reporter gene expression. Mol Imaging Biol. 2008;10:82–91
  18. Alauddin MM, Conti PS, Fissekis JD. Synthesis of [18F]-labeled 2′-deoxy-2′-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil ([18F]-FMAU). J Label Compd Radiopharm. 2002;45:583–590
  19. Alauddin MM, Conti PS, Fissekis JD. A general synthesis of 2′-deoxy-2′-[18F]fluoro-1-beta-d-arabinofuranosyluracil and its 5-substituted nucleosides. J Label Compd Radiopharm. 2003;46:285–289
  20. Alauddin MM, Conti PS, Fissekis JD, Watanabe KA. Synthesis of 2′-deoxy-2′-fluoro-1-beta-d-arabinofuranosyl uracil derivatives: a method suitable for preparation of [18F]-labeled nucleosides. Synth Commun. 2002;32:1757–1764
  21. Mangner TJ, Klecker RW, Anderson L, Shields AF. Synthesis of 2′-deoxy-2′-[18F]fluoro-beta-d-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU. Nucl Med Biol. 2003;30:215–224
  22. Balatoni J, Doubrovin M, Ageyeva L, Pillarsetty N, Finn R, Gelovani J, et al. Imaging herpes viral thymidine kinase-1 reporter gene expression with a new 18F-labeled probe: 2′-fluoro-2′-deoxy-5-[18F]fluoroethyl-1-beta-d-arabinofuranosyl uracil. Nucl Med Biol. 2005;32:811–819
  23. Chacko AM, Qu W, Kung H. Novel C-5 [18F]fluoroalkylated nucleosides for PET imaging of HSV1-tk gene expression. J Nucl Med. 2008;49:12P
  24. Chacko AM, Qu W, Kung HF. Synthesis and in vitro evaluation of 5-[18F]fluoroalkyl pyrimidine nucleosides for molecular imaging of herpes simplex virus type 1 thymidine kinase reporter gene expression. J Med Chem. 2008;51:5690–5701
  25. Chacko AM, Qu W, Kung HF. Synthesis of 5-fluoroalkylated pyrimidine nucleosides via Negishi cross-coupling. J Org Chem. 2008;73:4874–4881
  26. Choi SR, Zhuang ZP, Chacko AM, Acton PD, Tjuvajev-Gelovani J, Doubrovin M, et al. SPECT Imaging of herpes simplex virus type1 thymidine kinase gene expression by [123I]FIAU. Acad Radiol. 2005;12:798–805
  27. Surti S, Karp JS, Perkins AE, Cardi CA, Daube-Witherspoon ME, Kuhn A, et al. Imaging performance of A-PET: a small animal PET camera. IEEE Trans Med Imaging. 2005;24:844–852
  28. Alauddin MM, Shahinian A, Conti PS. Evaluation of 2′-deoxy-2′-fluoro-5-substituted-1-beta-d-arabinofuranosyluracils as markers for suicide gene expression in cancer cells. J Nucl Med. 2005;46:35P
  29. Issa W, Tochon-Danguy HJ, Lambert J, Sachinidis JI, Ackermann U, Liu Z, et al. Synthesis and evaluation of a thymidine analog for positron emission tomography study of tumor DNA proliferation in vivo. Nucl Med Biol. 2004;31:839–849

 This work was supported by a grant awarded from the National Institutes of Health (R21-EB-005242) to H.F.K. A travel award to A.-M.C. from the Educational Research Fund of the Society of Nuclear Medicine (SNM) supported the presentation of the preliminary results at the 2008 SNM Annual Meeting in New Orleans, LA.

PII: S0969-8051(08)00204-7

doi: 10.1016/j.nucmedbio.2008.10.009

Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 29-38 , January 2009