Département de chimie moléculaire

The purpose of this study was to develop a clin. relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclin. evaluation of a new positron emission tomog. (PET) imaging probe, 64Cu-labeled cyclam-RAFT-c(-RGDfK-)4 peptide (64Cu-RAFT-RGD), using this model. Varying degrees of $\alpha$v$\beta$3 integrin expression in several human pancreatic cancer cell lines were examd. by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP), was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclin. PET imaging coregistered with contrast-enhanced computed tomog. (CECT) comparing 64Cu-RAFT-RGD and 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in tumor, postimaging autoradiog., and histol. and immunohistochem. examns. were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly $\alpha$v$\beta$3 integrin specific. 64Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiog., histol., and immunohistochem. examns. confirmed the accumulation of 64Cu-RAFT-RGD in tumor vs. nontumor tissues. In comparative PET studies, 64Cu-RAFT-RGD accumulation provided better tumor contrast to background than 18F-FDG. Our results suggest that 64Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of $\alpha$v$\beta$3 integrin-expressing pancreatic tumors. [on SciFinder(R)]