Pancreatic adenocarcinoma is one (1) of the most lethal cancers in the United States, with an average survival of 3 to 6 months from the time of diagnosis. Currently available treatments have had little impact on the course of the disease. The goal of this research plan is to incorporate molecular imaging and image-guided interventional techniques to develop a new approach for the treatment of pancreatic cancer by using intratumoral injection of an attenuated measles virus (MV-Edm) genetically modified with the sodium-iodide symporter (NIS) gene (MV-NIS). MV-Edm was chosen for these studies because 1) MV-Edm infection causes massive cell-cell fusion, leading to a potent oncolytic effect in multiple human tumor models, and 2) NIS gene expression allows radioiodine-based in vivo imaging and therapy strategies. The propensity for local tumor invasion makes pancreatic cancer a compelling target for intratumoral gene delivery, owing to the potential value of local therapy. Our overall hypothesis is that image-guided intratumoral MV-NIS therapy combined with in vivo imaging of gene expression and therapeutic response will facilitate the development of genetically based therapies for pancreatic cancer.
The specific aims are to 1) determine the sensitivity and resolution of radioiodine-based imaging techniques for in vivo monitoring of MV-NIS infection and gene expression in pancreatic cancer xenografts, 2) use these imaging techniques to determine the efficiency and enhance the uniformity of intratumoral MV-NIS delivery, and 3) determine the utility of NIS as a therapuetic transgene for 131 l radiovirotherapy. The proposed career development plan combines didactic course work in molecular medicine and gene therapy with a supervised laboratory-based research experience. The long-term goals are to 1) develop an independent laboratory-based and translational research career in image-guided cancer gene therapy, and 2) translate the results of our laboratory research into appropriate clinical trials and therapeutic strategies for patients who have locally advanced or metastatic pancreatic carcinoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA103859-03
Application #
7232121
Study Section
Subcommittee G - Education (NCI)
Program Officer
Myrick, Dorkina C
Project Start
2005-06-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
3
Fiscal Year
2007
Total Cost
$131,220
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Penheiter, Alan R; Dingli, David; Bender, Claire E et al. (2012) Monitoring the initial delivery of an oncolytic measles virus encoding the human sodium iodide symporter to solid tumors using contrast-enhanced computed tomography. J Gene Med 14:590-7
Penheiter, Alan R; Russell, Stephen J; Carlson, Stephanie K (2012) The sodium iodide symporter (NIS) as an imaging reporter for gene, viral, and cell-based therapies. Curr Gene Ther 12:33-47
Penheiter, Alan R; Wegman, Troy R; Classic, Kelly L et al. (2010) Sodium iodide symporter (NIS)-mediated radiovirotherapy for pancreatic cancer. AJR Am J Roentgenol 195:341-9
Carlson, Stephanie K; Classic, Kelly L; Hadac, Elizabeth M et al. (2009) Quantitative molecular imaging of viral therapy for pancreatic cancer using an engineered measles virus expressing the sodium-iodide symporter reporter gene. AJR Am J Roentgenol 192:279-87
Carlson, Stephanie K; Classic, Kelly L; Bender, Claire E et al. (2007) Small animal absorbed radiation dose from serial micro-computed tomography imaging. Mol Imaging Biol 9:78-82
Carlson, Stephanie K; Classic, Kelly L; Hadac, Elizabeth M et al. (2006) In vivo quantitation of intratumoral radioisotope uptake using micro-single photon emission computed tomography/computed tomography. Mol Imaging Biol 8:324-32