1. ¹Department of Molecular & Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
2. ²The Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
3. ³Department of Radiology Bio-X program, Stanford University School of Medicine, USA
4. ⁴The Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
5. ⁵UCLA/DOE Laboratory of Structural Biology & Molecular Medicine, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
6. ⁶Molecular Biology Institute, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
7. ⁷UCLA-Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90095-1770, USA
8. ⁸Department of Biomathematics, UCLA School of Medicine, Los Angeles, California 90095-1770, USA

Correspondence: Professor Sanjiv S Gambhir, MD, PhD, Stanford University School of Medicine, The James H. Clark Center, 318 Campus Dr, E150, Stanford, CA 94305-5427, USA. E-mail: sgambhir@stanford.edu

Received 27 March 2004; Published online 10 December 2004.

Abstract

Molecular imaging of a suicide transgene's expression will aid the development of efficient and precise targeting strategies, and imaging for cancer cell viability may assess therapeutic efficacy. We used the PET reporter probe, 9-(4-[¹⁸F]fluoro-3-(hydroxymethyl)butyl)guanine ([¹⁸F]FHBG) to monitor the expression of a mutant Herpes Simplex Virus 1 thymidine kinase (HSV1-sr39tk) in C6 glioma tumors implanted subcutaneously in nude mice that were repetitively being treated with the pro-drug Ganciclovir (GCV). [¹⁸F]-Fluorodeoxyglucose ([¹⁸F]FDG), a metabolic tracer, was used to assess tumor cell viability and therapeutic efficacy. C6 glioma tumors stably expressing the HSV1-sr39tk gene (C6sr39) accumulated [¹⁸F]FHBG prior to GCV treatment. Significant declines in C6sr39 tumor volumes and [¹⁸F]FHBG and [¹⁸F]FDG accumulation were observed following 2 weeks of GCV treatment. However, 3 weeks after halting GCV treatment, the tumors re-grew and [¹⁸F]FDG accumulation increased significantly; in contrast, tumor [¹⁸F]FHBG concentrations remained at background levels. Therefore, [¹⁸F]FHBG can be used to detect tumors expressing HSV1-sr39tk, susceptible to regression in response to GCV exposure, and the effectiveness of GCV therapy in eradicating HSV1-sr39tk-expressing cells can be monitored by [¹⁸F]FHBG scanning. [¹⁸F]FHBG and [¹⁸F]FDG imaging data indicate that exposure of C6sr39 tumors to GCV causes the elimination of [¹⁸F]FHBG-accumulating C6sr39 cells and selects for re-growth of tumors unable to accumulate [¹⁸F]FHBG.