PET IMAGING OF ONCOLYTIC VSV EXPRESSING THE MUTANT HSV-1 THYMIDINE KINASE TRANSGENE IN A PRECLINICAL HCC RAT MODE
Kim A Muñoz-Álvarez, Jennifer Altomonte, Iina Laitinen, Sibylle Ziegler, Katja Steiger, Irene Esposito, Roland M Schmid1 and Oliver Ebert. (17-02-2015).The American Society of Gene & Cell Therapy, 2015, doi:10.1038/mt.2015.12
Research Area A
Hepatocellular carcinoma (HCC) is the most predominant form of liver cancer and the third leading cause of cancerrelated death worldwide. Due to the relative ineffectiveness of conventional HCC therapies, oncolytic viruses have emerged as novel alternative treatment agents. Our previous studies have demonstrated significant prolongation of survival in advanced HCC in rats after oncolytic vesicular stomatitis virus (VSV) treatment. In this study, we aimed to establish a reporter system to reliably and sensitively image VSV in a clinically relevant model of HCC for clinical translation. To this end, an orthotopic, unifocal HCC model in immune-competent Buffalo rats was employed to test a recombinant VSV vector encoding for an enhanced version of the herpes simplex virus 1 (HSV-1) thymidine kinase (sr39tk) reporter, which would allow the indirect detection of VSV via positron emission tomography (PET). The resulting data revealed specific tracer uptake in VSV-HSV1-sr39tk–treated tumors. Further characterization of the VSV-HSV1-sr39tk vector demonstrated its optimal detection time-point after application and its detection limit via PET. In conclusion, oncolytic VSV expressing the HSV1-sr39tk reporter gene allows for highly sensitive in vivo
imaging via PET. Therefore, this imaging system may be directly translatable and beneficial in further clinical applications. Received 8 August 2014; accepted 12 January 2015; advance onlinepublication 17 February 2015. doi:10.1038/mt.2015.