Micro-Positron Emission Tomography/Contrast-Enhanced Computed Tomography Imaging of Orthotopic Pancreatic Tumor-Bearing Mice Using the αvβ3 Integrin Tracer 64Cu-Labeled Cyclam-RAFT-c(-RGDfK-)4
Micro-Positron Emission Tomography/Contrast-Enhanced Computed Tomography Imaging of Orthotopic Pancreatic Tumor-Bearing Mice Using the αvβ3 Integrin Tracer 64Cu-Labeled Cyclam-RAFT-c(-RGDfK-)4
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DOI：
10.2310/7290.2013.00054
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发表时间：
2013-09-01
影响因子：
2.8
通讯作者：
Saga, Tsuneo
中科院分区：
文献类型：
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作者：
Aung, Winn;Jin, Zhao-Hui;Saga, Tsuneo
本研究的目的是开发一种临床相关的胰腺癌原位异种移植模型，并使用该模型对新型正电子发射断层扫描 (PET) 成像探针 Cu-64 标记的 cyclam-RAFT-c(-RGDfK-)(4) 肽 (Cu-64-RAFT-RGD) 进行临床前评估。通过流式细胞术和蛋白质印迹法检查了几种人胰腺癌细胞系中不同程度的α(v)β(3)整合素表达。细胞系 BxPC-3 稳定转染红色荧光蛋白 (RFP)，用于手术原位植入。在受体裸鼠的胰腺中建立原位异种移植物。进行了体内探针生物分布和受体阻断研究、临床前 PET 成像与对比增强计算机断层扫描 (CECT) 联合比较 Cu-64-RAFT-RGD 和 F-18-氟-2-脱氧-D-葡萄糖 (F-18-FDG) 在肿瘤中的积累、成像后放射自显影以及组织学和免疫组织化学检查。通过阻断研究进行的生物分布评估证实，探针与肿瘤的有效结合具有高度的 α(v)β(3) 整合素特异性。 Cu-64-RAFT-RGD PET 与 CECT 相结合，可以精确、轻松地检测癌症病变。放射自显影、组织学和免疫组织化学检查证实了肿瘤组织与非肿瘤组织中 Cu-64-RAFT-RGD 的积累。在比较 PET 研究中，Cu-64-RAFT-RGD 积累提供了比 F-18-FDG 更好的肿瘤背景对比度。我们的结果表明 Cu-64-RAFT-RGD PET 成像可能适用于诊断表达 α(v)β(3) 整合素的胰腺肿瘤。
The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET) imaging probe, Cu-64-labeled cyclam-RAFT-c(-RGDfK-)(4) peptide (Cu-64-RAFT-RGD), using this model. Varying degrees of alpha(v)beta(3) integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP), was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT) comparing Cu-64-RAFT-RGD and F-18-fluoro-2-deoxy-D-glucose (F-18-FDG) accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly alpha(v)beta(3) integrin specific. Cu-64-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of Cu-64-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, Cu-64-RAFT-RGD accumulation provided better tumor contrast to background than F-18-FDG. Our results suggest that Cu-64-RAFT-RGD PET imaging is potentially applicable for the diagnosis of alpha(v)beta(3) integrin-expressing pancreatic tumors.