843. MicroPET Imaging of HSV-TK Activity To Assess Cancer-Specific Gene Expression Targeted at the Level of Protein Translation Initiation

Abstract

Current cancer gene therapies are hindered by poor gene delivery and lack of tumor specificity. In order to enhance tumor specificity, the therapeutic suicide gene HSV-1 thymidine kinase (TK) sequence was modified with a 5’ upstream-untranslated region (5’-UTR) from the rat bFGF mRNA. This modification restricts protein translation of the suicide gene and cytotoxicity to cancer cells previously shown to express high levels of the translation initiation factor eIF4E. MicroPET scans utilizing a MicroPET rodent four-ring system (modelR4) from CTI Concord Microsystems, LLC (Knoxville, TN) imaging the radiolabled HSV1-TK substrate 18F-penciclovir were used to test suicide gene delivery and selective expression in tumor cells with in vitro cell cultures and in vivo animal models.