Tumor-specific in vivo transfection with HSV-1 thymidine kinase gene using a Sindbis viral vector as a basis for prodrug ganciclovir activation and PET.

Abstract

The vector efficiently targets the HSVtk enzyme gene into Sindbis-infected tumor cells. High levels of HSVtk expression ensure sufficient prodrug GCV conversion and activation for bystander effects that killed many surrounding untransduced tumor cells. In addition, the HSVtk activities in tumors can be noninvasively monitored using PET after systemic Sindbis/tk treatments as a basis for determining the levels and tissue distribution of vector, noninvasively in living animals, and for optimizing in vivo transfection rates of tumor.