title: PET imaging of oncolytic VSV expressing the mutant HSV-1 thymidine kinase transgene in a preclinical HCC rat model.
abstract: Hepatocellular carcinoma (HCC) is the most predominant form of liver cancer and the third leading cause of cancer-related 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.
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Muñoz-Álvarez
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Altomonte
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, München, Germany.
authors.forename: Iina
authors.initials: I
authors.lastname: Laitinen
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, München, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, München, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.affiliation: Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, München, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.affiliation: II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ebert
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging*; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging*; D008297:Male; D009154:Mutation; D050130:Oncolytic Virotherapy; D049268:Positron-Emission Tomography; D051381:Rats; D013937:Thymidine Kinase / Q000235:genetics*; D018116:Vesiculovirus
chemical_list: D013937:Thymidine Kinase