In vivo evaluation of 2'-deoxy-2'-[(18)F]fluoro-5-iodo-1-beta-D-arabinofuranosyluracil ([18F]FIAU) and 2'-deoxy-2'-[18F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil ([18F]FEAU) as markers for suicide gene expression.

Abstract

FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [14C]FIAU and [3H]FEAU. PET imaging was performed using [18F]FIAU and [18F]FEAU. In vitro uptake of [14C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p<0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [3H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p<0.001) than in wild type cells at the same time points. In vivo uptake of [14C]FIAU at 2 h in HSV1-tk positive tumors was 15.48+/-3.94, 6.7-fold higher (p<0.001) than in wild type tumors. Uptake of [3H]FEAU in transduced tumors was 9.98+/-1.99, 5.0-fold higher (p<0.001) than in wild type tumors. Micro-PET images using [18F]FIAU and [18F]FEAU also showed very high uptake in HSV-tk tumors. [18F]FIAU and [18F]FEAU appear to be potential PET imaging agents for gene expression.