In vivo spect imaging with 111In-dota-c(RGDfK) to detect early pancreatic cancer in a hamster pancreatic carcinogenesis model

摘要

Early detection of pancreatic cancer is key to overcoming its poor prognosis. αvβ3-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,N',N'',N'''-tetraacetic acidcyclo-( Arg-Gly-Asp-D-Phe-Lys) [ 111In-DOTA-c(RGDfK)], an imaging probe of αvβ3-integrin, for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesismodel. 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 tumorto- normal pancreatic tissue radioactivity ratios in excised pancreatic samples were measured with autoradiography (ARG) and compared with the immunopathologic findings for αvβ3-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 as3mmindiameter. 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 αvβ3-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.