MicroPET/CT imaging of orthotopic pancreatic tumor-bearing mice using the integrin tracer 64Cu-labeled cyclam-RAFT-c(-RGDfK-)4 peptide

Objective: Pancreatic cancer has the worst prognosis among solid tumors. Early diagnosis and efficient therapeutic measure remain as the major challenges. A suitable animal model that mimics the clinical situation as closely as possible is essential for developing and comparing new diagnostic and therapeutic strategies. A new PET imaging probe, 64Cu-labeled cyclam-RAFT-c(-RGDfK-)4 (64Cu-RAFT-RGD) peptide has been examined for visualization and quantification of avB3 integrin expression in animal tumor models by our group. The purpose of this study is to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer that reflects the clinical situation and to perform preclinical evaluation of 64Cu-RAFT-RGD probe, allowed in this model. Methods: Expression of avB3 integrin in several human pancreatic cancer cell lines was examined by flow cytometry and Western blotting. The representative cell line BxPC-3 which was stably transfected with red fluorescence reporter protein (RFP) that could be detected with optical imaging system, was used for surgical orthotopic implantation. In vivo probe biodistribution and receptor blocking study, preclinical PET imaging co-registered with contrast enhanced computed tomography (CECT) comparing 64Cu-RAFT-RGD and 18F-FDG accumulation in tumor, post imaging ex vivo autoradiography and histological examination were done. Results: Most of pancreatic cancer cell lines showed integrin avB3 expression. Orthotopic xenograft was established in pancreas of recipient nude mice by implantation of a piece of subcutaneous tumor developed in donor mice. In vivo biodistribution with blocking study confirmed that the efficient binding of probe to tumor is highly avB3 integrin specific. 64Cu-RAFT-RGD PET imaging combined with CECT that provided anatomical delineation of tumor, encouraged for precise and easy detection of pancreatic cancer lesion. In comparative PET study, 64Cu-RAFT-RGD accumulation provided better tumor contrast to background than 18F-FDG. Post imaging autoradiography and histological examination validated the accumulation of 64Cu-RAFT-RGD probe in tumor versus non-tumor tissues. Conclusion: Our results suggest that 64Cu-RAFT-RGD PET imaging can be potentially applicable for the diagnosis of avB3-expressing pancreatic cancer.2012 World Molecular Imaging Congres