PET of Cardiac Transgene Expression: Comparison of 2 Approaches Based on

PET of reporter gene expression holds promise for noninvasive monitoring of gene therapy. Previously, 2 approaches based on the herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) have been successfully applied to the heart. Wild-type HSV1-tk was imaged with 124I-labeled 2-fluoro-2-deoxy-5-iodo-1--D-arabinofuranosyl-5-iodouracil (FIAU), and a mutant HSV1-tk (HSV1-sr39tk) was imaged with 18F-labeled 9-[4-fluoro-3-(hy-droxymethyl)butyl]guanine (FHBG). The aim of this study was to compare these 2 combinations with regard to specificity, imag-ing contrast, and reporter probe kinetics using dynamic PET in small and large animals. Methods: Similar titers of adenovirus-expressing wild-type HSV1-tk (Adtk), mutant HSV1-sr39tk (Adsr39tk), or control genes were directly injected into the myo-cardium of 24 rats and 8 pigs. Two days later, dynamic PET was performed with a clinical scanner during the 120 min afte