Multimodal molecular imaging of integrin avb3 for in vivo detection of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of α_vβ₃ integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models. Methods: Immunohistochemistry and Western blot were used for characterization of α_vβ₃ expression in murine and human PDAC.We applied IntegriSense 680 fluorescencemolecular tomography, intraoperative fluorescence imaging, and ⁶⁸Ga-NODAGA-RGD PET for α_vβ₃ integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a^+/Cre;Kras ^{+/LSL-G12D;p53LoxP/LoxP} mice. (NODAGA is 1,4,7-triazacyclononane- 1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine- glycine-aspartic acid.) Results: α_vβ₃ integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and ⁶⁸Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders. Conclusion: Imaging approaches targeting α_vβ₃ integrin expand the potential of molecular imaging for identification of α_vβ₃-positive PDAC with potential implications in early detection, fluorescenceguided surgery, and therapy monitoring.