用 111In-DOTA-c(RGDfK)进行体内 SPECT 成像，以检测仓鼠胰腺癌发生模型中的早期胰腺癌。

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

机构信息

Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

J Nucl Med. 2012 May;53(5):765-71. doi: 10.2967/jnumed.111.099630. Epub 2012 Apr 10.

DOI:10.2967/jnumed.111.099630

PMID:22496584

Abstract

UNLABELLED

Early detection of pancreatic cancer is key to overcoming its poor prognosis. α(v)β(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 (111)In-1,4,7,10-tetraazacylododecane-N,N',N″,N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-d-Phe-Lys) [(111)In-DOTA-c(RGDfK)], an imaging probe of α(v)β(3)-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 (111)In-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 α(v)β(3)-integrin. In a mouse model in which inflammation was induced with turpentine, the uptake of (111)In-DOTA-c(RGDfK) in inflammatory regions was evaluated with ARG and compared with that of (18)F-FDG.

RESULTS

(111)In-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 (111)In-DOTA-c(RGDfK) strongly correlated with α(v)β(3)-integrin expression. In the inflammatory model, inflammation-to-muscle ratios for (18)F-FDG and (111)In-DOTA-c(RGDfK) were 8.37 ± 4.37 and 1.98 ± 0.60, respectively. These results imply that (111)In-DOTA-c(RGDfK) has a lower rate of false-positive tumor detection than (18)F-FDG.

CONCLUSION

Our findings suggest that SPECT with (111)In-DOTA-c(RGDfK) has great potential for the early and accurate detection of pancreatic cancer.

摘要

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早期发现胰腺癌是克服其预后不良的关键。α(v)β(3)-整联蛋白在胰腺肿瘤细胞中常过度表达，而在正常胰腺细胞中则很少表达。在这项研究中，我们研究了 SPECT 成像用 (111)In-1,4,7,10-四氮杂环十二烷-N,N',N″,N'''-四乙酸环-(Arg-Gly-Asp-d-Phe-Lys)[(111)In-DOTA-c(RGDfK)]，作为 α(v)β(3)-整联蛋白的成像探针，在仓鼠胰腺癌变模型中对胰腺癌的早期检测的有用性。

方法

用 N-亚硝基双(2-氧丙基)胺皮下注射诱导仓鼠胰腺导管癌，诱导胰腺癌。用 N-亚硝基双(2-氧丙基)胺处理的仓鼠进行体内 (111)In-DOTA-c(RGDfK)SPECT。成像后，通过放射性自显影 (ARG)测量切除的胰腺样本中肿瘤与正常胰腺组织的放射性比值，并与α(v)β(3)-整联蛋白的免疫病理发现进行比较。在使用松节油诱导炎症的小鼠模型中，通过 ARG 评估炎症部位 (111)In-DOTA-c(RGDfK)的摄取，并与 (18)F-FDG 的摄取进行比较。

结果

直径为 3mm 的小胰腺癌病变可清晰显示 (111)In-DOTA-c(RGDfK)。ARG 分析显示，肿瘤与正常胰腺组织的放射性比值较高（腺癌为 4.6 ± 1.0，非典型增生为 3.3 ± 1.4）。(111)In-DOTA-c(RGDfK)的摄取与α(v)β(3)-整联蛋白的表达密切相关。在炎症模型中，(18)F-FDG 和 (111)In-DOTA-c(RGDfK)的炎症与肌肉比值分别为 8.37 ± 4.37 和 1.98 ± 0.60。这些结果表明，与 (18)F-FDG 相比，(111)In-DOTA-c(RGDfK)具有更低的假阳性肿瘤检测率。