RT Journal Article
SR Electronic
T1 In Vivo SPECT Imaging with <sup>111</sup>In-DOTA-c(RGDfK) to Detect Early Pancreatic Cancer in a Hamster Pancreatic Carcinogenesis Model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 765
OP 771
DO 10.2967/jnumed.111.099630
VO 53
IS 5
A1 Mitsuyoshi Yoshimoto
A1 Takuya Hayakawa
A1 Michihiro Mutoh
A1 Toshio Imai
A1 Keisuke Tsuda
A1 Sadaaki Kimura
A1 Izumi O. Umeda
A1 Hirofumi Fujii
A1 Keiji Wakabayashi
YR 2012
UL http://jnm.snmjournals.org/content/53/5/765.abstract
AB 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 acid-cyclo-(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 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 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 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 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.