An Integrin-alpha(v)beta(6)/alpha(5)beta(1)-Bitargeted Probe for the SPECT Imaging of Pancreatic Adenocarcinoma in Preclinical and Primary Clinical Studies
An Integrin-alpha(v)beta(6)/alpha(5)beta(1)-Bitargeted Probe for the SPECT Imaging of Pancreatic Adenocarcinoma in Preclinical and Primary Clinical Studies
复制标题
用于临床前和初步临床研究中胰腺腺癌 SPECT 成像的整合素-α(v)β(6)/α(5)β(1) 双靶向探针
DOI：
10.1021/acs.bioconjchem.1c00296
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发表时间：
2021
影响因子：
4.7
通讯作者：
Wang Fan
中科院分区：
文献类型：
--
作者：
Zhao Haitao;Gao Hannan;Luo Chuangwei;Yang Guangjie;Zhao Xiaoyu;Gao Shi;Ma Qingjie;Jia Bing;Shi Jiyun;Wang Fan
胰腺腺癌（PA）是最致命的人类恶性肿瘤之一。然而，目前临床常规影像学技术对PA的早期发现、手术可切除性预测和预后具有挑战性。分子成像技术结合新型成像探针可用于早期发现和准确分期。在PA中发现整合素αvβ6和α5β1过表达。本研究制备了整合素αvβ6/α5β1靶向探针99mtc - hynic - isodgr （99mTc-isoDGR）和99mtc - hynic - peg4 - pisodgr2 (99mTc-3PisoDGR2)，并在BxPC-3人胰腺肿瘤模型中进行了评价。99mtc - isodgr纳米扫描SPECT/CT可清晰显示皮下和皮下bxpc -3肿瘤，肿瘤与背景之比高。过量非放射性肽阻断研究显示肿瘤摄取明显减少，证实了99mtc - isodgr的特异性。生物分布结果证实了成像结果。与99mtc - isodgr相比，二聚体示踪剂99mtc - 3pisodgr2显著增强了肿瘤摄取，并且99mtc - 3pisodgr2可以清晰地显示小鼠模型中自发性PA病变。初步临床研究也验证了99mtc - 3pisodgr2检测PA的能力。因此，利用整合素αvβ6/α5β1-bitargeted99mTc-3PisoDGR2进行SPECT/CT成像，为PA的无创检测提供了一种潜在的方法。
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 αvβ6and α5β1are found to be overexpressed in PA. In this study, integrin αvβ6/α5β1-bitargeted probes99mTc-HYNIC-isoDGR (99mTc-isoDGR) and99mTc-HYNIC-PEG4-PisoDGR2 (99mTc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous andin situBxPC-3 tumors could be clearly visualized by99mTc-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 of99mTc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer99mTc-3PisoDGR2 significantly enhanced tumor uptake compared with99mTc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by99mTc-3PisoDGR2. The primary clinical study also verified the ability of99mTc-3PisoDGR2 for detection of PA. Therefore, SPECT/CT imaging using the integrin αvβ6/α5β1-bitargeted99mTc-3PisoDGR2 provided a potential approach for the noninvasive detection of PA.