Abstract
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Objectives αvβ3 integrin is expressed in human pancreatic cancer. We investigated the usefulness of 111In-DOTA-c(RGDfK) for early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model.
Methods To induce pancreatic cancer, hamsters were subcutaneously injected with N-nitrosobis(2-oxopropyl)amine (BOP) as a carcinogen at 10 mg/kg body weight. Expression of αvβ3 integrin in normal pancreatic duct, hyperplasia, atypical hyperplasia and adenocarcinoma was examined by immunohistochemistry. Hamsters from 20 weeks after BOP treatment were injected in subclavian vein with 19.3 - 33.7 MBq of 111In-DOTA-c(RGDfK). SPECT/CT imaging was performed at 60 min post-injection using NanoSPECT/CT (Bioscan). After the SPECT scan, ex vivo autoradiograpy (ARG) and pathological analysis (HE and αvβ3 integrin staining) were carried out.
Results αvβ3 integrin was strongly expressed in hyperplasia, atypical hyperplasia and adenocarcinoma. SPECT imaging clearly visualized pancreatic cancers in the hamster model. In this model, apparent accumulation of radioactivity in liver was not observed. Furthermore, 111In-DOTA-c(RGDfK) was not taken up in purulent inflammatory lesions. ARG images revealed that 111In-DOTA-c(RGDfK) accumulated in atypical hyperplasia. High expression ofαvβ3 integrin was found in accord with the hot spots of 111In-DOTA-c(RGDfK). From ARG analysis, tumor to normal pancreas (T/N) ratios were 4.6 ± 1.0 in adenocarcinoma and 3.3 ± 1.4 in atypical hyperplasia. On the other hand, inflammation to normal pancreas ratio was 0.9.
Conclusions 111In-DOTA-c(RGDfK) demonstrated the specific accumulation in pancreatic cancer and the high T/N ratios, resulting in clear delineation of pancreatic cancer in a hamster pancreatic carcinogenesis model. SPECT imaging using 111In-DOTA-c(RGDfK) has great potential for early and accurate detection of pancreatic cancer