In Vivo SPECT Imaging with 111In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model

摘要

id="p-2">Early detection of pancreatic cancer is key to overcoming its poor prognosis. ?±_v?2₃-integrin is often overexpressed in pancreatic tumor cells, whereas it is scarcely expressed in normal pancreatic cells. In this study, we investigated the usefulness of SPECT imaging with 111In-1,4,7,10-tetraazacylododecane-N,Na€2,Na€3,Na€2a€2a€2-tetraacetic acid-cyclo-(Arg-Gly-Asp- class="sc">d-Phe-Lys) [111In-DOTA-c(RGDfK)], an imaging probe of ?±_v?2₃-integrin, for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. >Methods: Hamsters were subcutaneously injected with the pancreatic duct carcinogen N-nitrosobis(2-oxopropyl)amine to induce pancreatic cancer. N-nitrosobis(2-oxopropyl)amine-treated hamsters underwent in vivo SPECT with 111In-DOTA-c(RGDfK). After imaging, the tumor-to-normal pancreatic tissue radioactivity ratios in excised pancreatic samples were measured with autoradiography (ARG) and compared with the immunopathologic findings for ?±_v?2₃-integrin. In a mouse model in which inflammation was induced with turpentine, the uptake of 111In-DOTA-c(RGDfK) in inflammatory regions was evaluated with ARG and compared with that of 18F-FDG. >Results: 111In-DOTA-c(RGDfK) was clearly visualized in pancreatic cancer lesions as small as 3 mm in diameter. ARG analysis revealed high tumor-to-normal pancreatic tissue radioactivity ratios (4.6 ?± 1.0 [mean ?± SD] in adenocarcinoma and 3.3 ?± 1.4 in atypical hyperplasia). The uptake of 111In-DOTA-c(RGDfK) strongly correlated with ?±_v?2₃-integrin expression. In the inflammatory model, inflammation-to-muscle ratios for 18F-FDG and 111In-DOTA-c(RGDfK) were 8.37 ?± 4.37 and 1.98 ?± 0.60, respectively. These results imply that 111In-DOTA-c(RGDfK) has a lower rate of false-positive tumor detection than 18F-FDG. >Conclusion: Our findings suggest that SPECT with 111In-DOTA-c(RGDfK) has great potential for the early and accurate detection of pancreatic cancer.