RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 637
OP 648
DO 10.2967/jnumed.107.046227
VO 49
IS 4
A1 Miyagawa, Tadashi
A1 Gogiberidze, George
A1 Serganova, Inna
A1 Cai, Shangde
A1 Balatoni, Julius A.
A1 Thaler, Howard T.
A1 Ageyeva, Lyudmila
A1 Pillarsetty, Nagavarakishore
A1 Finn, Ronald D.
A1 Blasberg, Ronald G.
YR 2008
UL http://jnm.snmjournals.org/content/49/4/637.abstract
AB 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.