Stephanie Kay Carlson MD, Presenter: Nothing to Disclose

Alan Penheiter PhD, Abstract Co-Author: Nothing to Disclose

David Dingli MD, PhD, Abstract Co-Author: Nothing to Disclose

Kelly Classic, Abstract Co-Author: Nothing to Disclose

Claire E. Bender MD, Abstract Co-Author: Nothing to Disclose

Troy R. Wegman, Abstract Co-Author: Nothing to Disclose

Guy E. Griesmann, Abstract Co-Author: Nothing to Disclose

Mark J. Federspiel, Abstract Co-Author: Nothing to Disclose

Yasuhiro Ikeda DVM, Abstract Co-Author: Nothing to Disclose

Stephen J. Russell MD, PhD, Abstract Co-Author: Inventor, Patent Application, Measle Virus-Sodium Iodide Symporter Gene

00030490-DMT et al, Abstract Co-Author: Nothing to Disclose

We have previously shown the therapeutic efficacy of an engineered oncolytic measles virus expressing the sodium iodide symporter reporter gene (MV-NIS) in human pancreatic cancer xenografts. The goal of this follow-up study was to determine the utility of NIS as a therapeutic gene for 131I-mediated radiotherapy in this same tumor model.

This study was approved by our Institutional Animal Care and Use Committee and used 74 nude mice. Subcutaneous human BxPC-3 pancreatic tumors were injected twice with MV-NIS (3.5 x 106 TCID50). Viral infection, NIS expression, and intratumoral iodide uptake were imaged and quantitated with 123I micro-SPECT/CT. Mice with MV-NIS infected tumors were then treated with 0, 1, or 2 mCi 131I and monitored for tumor progression and survival up to 90 days. Control groups included mice with BxPC-3 tumors and no treatment, and mice with BxPC-3 tumors treated with MV-NIS only. Additional studies were performed with stable NIS-expressing xenografts (BxPC-3-NIS) created by infecting BxPC-3 cells with a self-inactivating bicistronic lentiviral vector containing human NIS. These groups of mice were treated with 0, 0.1, 0.5, 1, or 2 mCi of 131I.

Intratumoral injection of MV-NIS resulted in significant delay in tumor growth and a significant prolongation of survival compared with non-treated mice (P ≤ 0.05). Synergy between MV-NIS induced oncolysis and NIS-mediated 131I ablation was not seen in this model. However, a significant correlation was observed between NIS-mediated intratumoral iodide (% ID/g) and peak tumor volume reduction with the combination of MV-NIS and 131I therapy. All tumors established with stable NIS-expressing BxPC-3 cells exhibited rapid regression with ≥ 0.5 mCi 131I (tumor dose = 4 Gy), indicating that the lack of synergy observed with combination MV-NIS and 131I was not due to a lack of radiosensitivity in this model.

NIS appears to be a valuable reporter for quantitative, non-invasive monitoring of oncolytic measles; however, significant hurdles exist for its use as a therapeutic gene for combined radiovirotherapy in this human pancreatic cancer model. Further preclinical work is required to increase intratumoral NIS-mediated iodide uptake and retention.

NIS is a useful imaging biomarker for following oncolytic viral therapy. 

Carlson, S, Penheiter, A, Dingli, D, Classic, K, Bender, C, Wegman, T, Griesmann, G, Federspiel, M, Ikeda, Y, Russell, S, et al, 0, Sodium Iodide Symporter (NIS) Gene-mediated Radiovirotherapy for Pancreatic Cancer.  Radiological Society of North America 2009 Scientific Assembly and Annual Meeting, November 29 - December 4, 2009 ,Chicago IL. http://archive.rsna.org/2009/8002609.html