RT Journal Article SR Electronic T1 Preclinical Evaluation of the Penciclovir Analog 9-(4-[18F]Fluoro-3-Hydroxymethylbutyl)Guanine for In Vivo Measurement of Suicide Gene Expression with PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1682 OP 1690 VO 42 IS 11 A1 Mian M. Alauddin A1 Antranik Shahinian A1 Erlinda M. Gordon A1 James R. Bading A1 Peter S. Conti YR 2001 UL http://jnm.snmjournals.org/content/42/11/1682.abstract AB The gene for herpes simplex virus thymidine kinase (HSV-tk) is widely used as a suicide gene in experimental gene therapy of cancer. 9-(4-Fluoro-3-hydroxymethylbutyl)guanine (FHBG) is an antiviral nucleoside analog that is rapidly phosphorylated by viral thymidine kinase but is a poor substrate for mammalian thymidine kinase. Recently, FHBG labeled in the 4-fluoro position with 18F has shown promise relative to other similar compounds for imaging in vivo expression of HSV-tk using PET. In this study, we evaluated the uptake of [18F]FHBG in vitro and in vivo using transduced and wild-type human colon cancer cells (HT-29). We also imaged [18F]FHBG and measured the radioactivity concentrations of circulating [18F]FHBG and its metabolites in monkeys. Methods: Sterile, pyrogen-free [18F]FHBG was produced routinely in good yields. Cells were transduced with the retroviral vector G1Tk1SvNa containing HSV-tk gene. In vitro uptake studies were performed by incubating cells with [18F]FHBG at 37°C for 1 and 5 h. Biodistribution studies were performed at 2 and 5 h after injection in nude mice bearing tumors grown from wild-type or transduced cells. Sequential, whole-body PET scans of cynomolgus monkeys were obtained over a period of >2 h after intravenous injection of [18F]FHBG. Arterial plasma samples obtained from monkeys 15–120 min after intravenous injection were subjected to acid extraction, and the acid-soluble fractions were analyzed by high-performance liquid chromatography. Results: In vitro studies showed 31 and 71 (P < 0.001) times higher uptake of the probe at 1 and 5 h, respectively, in transduced cells compared with nontransduced cells. In vivo studies in mice showed that tumor uptake of the radiotracer was 4-fold (P < 0.05) and 13-fold (P < 0.001) higher at 2 and 5 h, respectively, in tumors grown from transduced cells compared with control cells. Transduced tumor-to-normal tissue ratios ranged from 2 to 25 at 2 h and from 2 to 22 at 5 h. Recirculating labeled metabolites had only a minor effect on the biodistribution of radiolabel from [18F]FHBG in monkeys. Conclusion: These results indicate that [18F]FHBG may yield high-contrast PET images of HSV-tk expression in tumors and, therefore, it is a very promising radiotracer for monitoring of gene therapy of cancer with PET.