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Early detection of pancreatic cancer is key to overcoming its poor prognosis. α^sub v^β^sub 3^-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) [^sup 111^In-DOTA-c(RGDfK)], an imaging probe of α^sub v^β^sub 3^-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 ^sup 111^In-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 α^sub v^β^sub 3^-integrin. In a mouse model in which inflammation was induced with turpentine, the uptake of ^sup 111^In-DOTA-c(RGDfK) in inflammatory regions was evaluated with ARG and compared with that of ^sup 18^F-FDG. Results: ^sup 111^In-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 ^sup 111^In-DOTA-c(RGDfK) strongly correlated with α^sub v^β^sub 3^-integrin expression. In the inflammatory model, inflammation- to-muscle ratios for ^sup 18^F-FDG and ^sup 111^In-DOTA-c(RGDfK) were 8.37 ± 4.37 and 1.98 ± 0.60, respectively. These results imply that ^sup 111^In-DOTA-c(RGDfK) has a lower rate of false-positive tumor detection than ^sup 18^F-FDG. Conclusion: Our findings suggest that SPECT with ^sup 111^In-DOTA-c(RGDfK) has great potential for the early and accurate detection of pancreatic cancer.
Key Words: 111In-DOTA-c(RGDfK); SPECT; α^sub v^β^sub 3^-integrin; pancreatic cancer; early detection
J Nucl Med 2012; 53:765-771
DOI: 10.2967/jnumed.111.099630
Pancreatic cancer is a leading cause of cancer-related mortality in developed countries, with an increasing incidence (1). The 5-y survival rate is poor (2,3). Surgical resection remains the only curative option. The postoperative 5-y survival rate has been recorded to be high as 40%-50%, whereas only 15%-20% of tumors are found to be resectable at the time of diagnosis (4). Tumor size is an important prognostic factor for pancreatic cancer because better prognosis and postsurgical survival have been reported for small pancreatic cancers (#2 cm) than for large ones (.2 cm) (5,6). Given the incidence and high mortality rate...