Evaluation of [18F]fluoroestradiol and ChRERα as a gene expression PET reporter system in rhesus monkey brain

Positron emission tomography (PET) reporter systems are a valuable means of estimating the level of expression of a transgene in vivo. For example, the safety and efficacy of gene therapy approaches to the treatment of neurological and neuropsychiatric disorders could be enhanced via the monitoring of exogenous gene expression levels in the brain. The present study evaluated the ability of a newly developed PET reporter system, [18F]fluoroestradiol, and the estrogen receptor-based PET reporter ChRERα to monitor expression levels of a shRNA designed to suppress choline acetyltransferase (ChAT) expression in rhesus monkey brain. The ChRERα gene and shRNA were delivered together in the same viral vector to monkey striatum. In two monkeys that received injections of viral vector, [18F]fluoroestradiol binding increased by 70% and 86%, respectively, at the target sites compared to pre-injection, demonstrating that ChRERα expression could be visualized in vivo with PET imaging. Postmortem immunohistochemistry confirmed that ChAT expression was significantly suppressed in regions in which [18F]fluoroestradiol uptake was increased. The consistency between PET imaging and immunohistochemical results suggests that [18F] fluoroestradiol and ChRERα can serve as a PET reporter system in rhesus monkey brain for in vivo evaluation of the expression of potential therapeutic agents, such as shRNAs.