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Model Organisms

Targeted Imaging of Colonic Tumors in Smad3^–/– Mice Discriminates Cancer and Inflammation

¹ Department of Surgery and Division of Surgical Oncology, ² Department of Radiology and the Vanderbilt University Institute of Imaging Science, ³ Vanderbilt Ingram Cancer Center and ⁴ Departments of Medicine and Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Departments of ⁵ Neurosurgery, ⁶ Chemistry, ⁷ Pathology, and ⁸ Pediatrics at the Cincinnati Children's Hospital and the University of Cincinnati College of Medicine, Cincinnati, Ohio; and ⁹ Department of Medicine and the Department of Veterans Affairs Medical Center, Nashville, TN

Requests for reprints: Darryl J. Bornhop, 5419 Stevenson VU Station B Box 351822, 1161 21st Avenue South, Nashville, TN 37235-1822. Phone: 615-322-4226. E-mail: Darryl.Bornhop{at}vanderbilt.edu

The peripheral benzodiazepine receptor (PBR) is a trans-mitochondrial membrane protein that modulates steroid biosynthesis. Recently, up-regulation and nuclear localization of PBR has been shown to be associated with colon, prostate, and breast cancer. PBR has been targeted by the exogenous synthetic ligand, PK11195, for various purposes including imaging. To capitalize on these observations, we developed a high-throughput, noninvasive, in vivo imaging approach to detect spontaneously arising colonic tumors in mice using a novel PBR-targeted molecular imaging agent (NIR-conPK11195). NIR-conPK11195 localized and was retained in colonic adenomas and carcinomas in Smad3^–/– mice but not in non-neoplastic hamartomas or chronically inflamed colonic tissue. Using a fluorescence signal-to-noise ratio of 4-fold 13 h after injection of the agent, we detected colonic tumors with a sensitivity of 67% and a specificity of 86% in a cohort of 37 Smad3^–/– mice and control littermates. Furthermore, using oral administration of dextran sulfate to induce colonic inflammation, we showed that the clearance profile of NIR-conPK11195 distinguished transient uptake in inflammatory tissue from longer term retention in tumors. Taken together, these results indicate that NIR-conPK11195 is a promising optical molecular imaging tool to rapidly screen for colonic tumors in mice and to discriminate inflammation from cancer. (Mol Cancer Res 2007;5(4):341–9)