Scintigraphic Imaging of HSVtk Expression in Gene Therapy

Suicide gene therapy is under investigation as a treatment for cancer. In this therapy, a suicide gene is introduced into tumor cells, enabling the conversion of a prodrug into a toxic metabolite that selectively kills the transfected tumor cells. In the most investigated strategy, the herpes simplex virus thymidine kinase (HSVtk) suicide gene is used in combination with the prodrug ganciclovir. To assess the efficiency and safety of gene therapy protocols, a noninvasive method to assay the magnitude, kinetics and spatial distribution of transgene expression is essential. Imaging methods for repetitive monitoring of HSVtk transgene expression in living animals and humans, using single photon emission computed tomography (SPECT) or positron emission tomography (PET), have been developed. For many therapeutic genes, however, no imaging method is available. In these cases, reporter genes can be applied. Expression of the therapeutic gene can be determined indirectly by imaging a reporter gene, like HSVtk, that is linked to the therapeutic gene. Reporter genes can also be applied to monitor the expression of endogenous genes and to track the fate of transplanted cells. This paper presents an updated review on the progress in the field of non-invasive nuclear imaging of HSVtk transgene expression in gene therapy.