Zhao Haitao, Gao Hannan, Luo Chuangwei, Yang Guangjie, Zhao Xiaoyu, Gao Shi, Ma Qingjie, Jia Bing, Shi Jiyun, Wang Fan
Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Bioconjug Chem. 2021 Jul 21;32(7):1298-1305. doi: 10.1021/acs.bioconjchem.1c00296. Epub 2021 Jun 17.
Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin αβ and αβ are found to be overexpressed in PA. In this study, integrin αβ/αβ-bitargeted probes Tc-HYNIC-isoDGR (Tc-isoDGR) and Tc-HYNIC-PEG-PisoDGR2 (Tc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and BxPC-3 tumors could be clearly visualized by Tc-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of Tc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer Tc-3PisoDGR2 significantly enhanced tumor uptake compared with Tc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by Tc-3PisoDGR2. The primary clinical study also verified the ability of Tc-3PisoDGR2 for detection of PA. Therefore, SPECT/CT imaging using the integrin αβ/αβ-bitargeted Tc-3PisoDGR2 provided a potential approach for the noninvasive detection of PA.
胰腺腺癌（PA）是最致命的人类恶性肿瘤之一。然而，在临床中，利用当前的传统成像技术对PA进行早期检测、手术可切除性预测和预后评估具有挑战性。分子成像技术与新型成像探针相结合可能有助于PA的早期检测和准确分期。研究发现整合素αβ和αβ在PA中过表达。在本研究中，制备了整合素αβ/αβ双靶点探针锝[Tc] - 高锝酸盐 - 异二肽甘氨酸受体（Tc - isoDGR）和锝[Tc] - 高锝酸盐 - 聚乙二醇 - 双异二肽甘氨酸受体2（Tc - 3PisoDGR2），并在BxPC - 3人胰腺肿瘤模型中进行评估。通过Tc - isoDGR纳米扫描单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）成像，皮下和BxPC - 3肿瘤均能清晰显示，肿瘤与背景比值高。用过量非放射性肽进行的阻断研究显示肿瘤摄取显著降低，这证实了Tc - isoDGR的特异性。生物分布结果证实了成像结果。与Tc - isoDGR相比，二聚体示踪剂Tc - 3PisoDGR2显著增强了肿瘤摄取，并且在小鼠模型中，Tc - 3PisoDGR2能够清晰显示自发性PA病变。初步临床研究也验证了Tc - 3PisoDGR2检测PA的能力。因此，使用整合素αβ/αβ双靶点的Tc - 3PisoDGR2进行SPECT/CT成像为PA的无创检测提供了一种潜在方法。
