Tumor-Specific In Vivo Transfection with HSV-1 Thymidine Kinase Gene Using a Sindbis Viral Vector as a Basis for Prodrug Ganciclovir

One type of gene therapy of tumors, gene-directed enzyme-prodrug therapy (GDEPT), holds considerable promise, although practical considerations limit its clinical applicability. These in-clude the lack of acceptable noninvasive methods that are adaptable to humans for selective tumor targeting of the thera-peutic genetic material. Sindbis virus is an oncolytic, a-virus that selectively targets tumors through the 67-kDa laminin recep-tor (LAMR). In this report we describe a novel approach that permits tumor-selective tumor targeting and quantitative in vivo monitoring using PET of a commonly applied GDEPT, based on herpes simplex virus thymidine kinase type 1 (HSVtk) and ganciclovir (GCV). Methods: Sindbis/tk vectors were harvested from the supernatant of in vitro cultures of a packaging cell pro-duced by electroporation of both replicon RNA (SinRep5/tk) and helper RNA (DH-BB) into baby hamster kidney (BHK) cells. Th