TY - JOUR T1 - Imaging of HSV-<em>tk</em> Reporter Gene Expression: Comparison Between [<sup>18</sup>F]FEAU, [<sup>18</sup>F]FFEAU, and Other Imaging Probes JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 637 LP - 648 DO - 10.2967/jnumed.107.046227 VL - 49 IS - 4 AU - Tadashi Miyagawa AU - George Gogiberidze AU - Inna Serganova AU - Shangde Cai AU - Julius A. Balatoni AU - Howard T. Thaler AU - Lyudmila Ageyeva AU - Nagavarakishore Pillarsetty AU - Ronald D. Finn AU - Ronald G. Blasberg Y1 - 2008/04/01 UR - http://jnm.snmjournals.org/content/49/4/637.abstract N2 - Herpes virus type 1 thymidine kinase (HSV1-tk) and the mutant HSV1-sr39tk are the 2 most widely used “reporter genes” for radiotracer-based imaging. Two pyrimidine nucleoside analogs, [18F]FEAU (1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-ethyluridine) and [18F]FFEAU (1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-(2-fluoroethyl)uridine), have generated recent interest as potential new probes for imaging HSV1-tk and HSV1-sr39tk gene expression. Methods: We compared [18F]FEAU and [18F]FFEAU with a series of other pyrimidine nucleoside derivatives (including 1-(2′-deoxy-2′-fluoro-β-d-arabinofuranosyl)-5-iodouridine [FIAU]) and with acycloguanosine analogs using a stable HSV1-tk transduced cell line (RG2TK+) and wild-type RG2 cells. Results: The in vitro accumulation data and the calculated and normalized clearance constant, nKi, as well as sensitivity and selectivity indices indicated that 2 pyrimidine nucleoside probes, [18F]FEAU and [18F]FFEAU, had the best uptake characteristics. These probes were selected for further dynamic PET studies in nude rats bearing subcutaneous RG2TK+ and RG2 tumors. The 2-h postinjection [18F]FEAU uptake levels were 3.3% ± 1.0% and 0.28% ± 0.07% dose/cm3 in subcutaneous RG2TK+ and RG2 tumors, respectively, and 2.3% ± 0.2% and 0.19% ± 0.01% dose/cm3, respectively, for [18F]FFEAU. The corresponding RG2TK+/RG2 uptake ratios were 11.5 ± 1.5 and 12.2 ± 1.4, respectively. The inherent problem of comparing different radiolabeled pyrimidine nucleoside and guanosine-based probes for imaging HSV1-tk expression using different transduced cell lines and assay systems in the absence of an independent thymidine kinase–enzyme assay is discussed. Conclusion: For HSV1-tk reporter systems that require a 1- to 4-h PET paradigm, HSV1-tk-[18F]FEAU is the current top contender. ER -