SPECT / CT Imaging of hNIS-Expression after Intravenous Delivery of an Oncolytic Adenovirus and I-131 Rajecki

Oncolytic adenoviruses can be engineered for better tumor selectivity, gene delivery and be armed for imaging and concentrating radionuclides into tumors for synergistic oncolysis. We constructed Ad5/3-hTERT-hNIS where replication is controlled by hTERT-promoter. Ad5/3-hTERT-hNIS expresses hNIS for imaging of transgene expression and for treatment of infected tumors by radioiodine. Ad5/3-hTERT-hNIS efficiently killed prostate cancer cells and induced iodine uptake in vitro and in vivo after intratumoral virus administration. Survival of mice treated with intravenous Ad5/3-hTERT-hNIS significantly prolonged survival over mock or radioiodine only but the combination of virus with radioiodine was not more effective than virus alone. Temporal and spatial changes in hNIS-expression during therapy were detected with SPECT, demonstrating feasibility of evaluation of the combination therapy with hNIS-expressing adenoviruses and radioiodide. Citation: Rajecki M, Sarparanta M, Hakkarainen T, Tenhunen M, Diaconu I, et al. (2012) SPECT/CT Imaging of hNIS -Expression after Intravenous Delivery of an Oncolytic Adenovirus and I. PLoS ONE 7(3): e32871. doi:10.1371/journal.pone. 0032871 Editor: Ilya Ulasov, University of Chicago, United States of America Received September 1, 2011; Accepted February 1, 2012; Published March 7, 2012 Copyright: 2012 Rajecki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The study was supported by the Helsinki Biomedical Graduate School (www.hbgs.helsinki.fi) and grants from Finnish Foundation for Research on Viral Diseases (www.virustauti.fi), Emil Aaltonen foundation (www.emilaaltonen.fi), Biomedicum Helsinki Foundation (www.biomedicum.fi), Irja Karvonen’s Cancer Foundation (www.karvonensaatio.fi), Jalmari and Rauha Ahokas Foundation (www.ahokkaansaatio.org), The Finnish Medical Foundation (www.laaketieteensaatio.fi), K. Albin Johansson Foundation (www.foundationweb.net/johansson/), Jenny and Antti Wihuri Foundation (www.wihurinrahasto.fi), Drug Discovery Graduate School (ddgs.utu.fi), European Research Council (erc.europa.eu), ASCO Foundation (www.asco.org), HUCH Research Funds (EVO), Sigrid Juselius Foundation (www.sigridjuselius.fi/foundation), Academy of Finland (www.aka.fi), Biocentrum Helsinki (www.helsinki.fi/biocentrum), Biocenter Finland (www. biocenter.fi) and University of Helsinki (www.helsinki.fi). Akseli Hemminki is K. Albin Johansson Research Professor of the Foundation for the Finnish Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: A. Hemminki is a co-founder and shareholder in Oncos Therapeutics ltd. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare. * E-mail: akseli.hemminki@helsinki.fi . These authors contributed equally to this work.