Clinical Translation of a 68Ga-Labeled Integrin αvβ6-Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer
Clinical Translation of a 68Ga-Labeled Integrin αvβ6-Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer
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68Ga 标记的整合素 αvβ6 靶向循环放射性示踪剂用于胰腺癌 PET 成像的临床转化
DOI：
10.2967/jnumed.119.237347
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发表时间：
2020-10-01
影响因子：
9.3
通讯作者：
Liu, Zhaofei
中科院分区：
文献类型：
--
作者：
Feng, Xun;Wang, Yanpu;Liu, Zhaofei
胰腺癌中整合素α（v）β（6）的过度表达使其成为非侵入性PET成像的有希望的靶点。然而，目前，大多数整联蛋白α（v）β（6）靶向放射性示踪剂是基于线性肽，其在血清中被蛋白酶快速降解。在此，我们的目的是开发和评估Ga-68标记的整合素α（v）β（6）靶向环肽（Ga-68-cybrandide）用于胰腺癌的PET成像。研究方法：制备Ga-68-cyclohide，并在整合素α（v）β（6）阳性BxPC-3人胰腺癌小鼠模型中将其PET成像曲线与线性肽（Ga-68-linear-pep）的PET成像曲线进行比较。5名健康志愿者（2名女性和3名男性）在注射Ga-68-cysteine后接受全身PET/CT成像，并计算生物分布和剂量学。对2例患者进行PET/CT成像，以探讨68 Ga-环磷酰胺在胰腺癌诊断和治疗监测中的潜在作用。结果如下：在BxPC-3荷瘤小鼠中，Ga-68-cybridde表现出比Ga-68-linear-pep显著更高的肿瘤摄取，这至少部分归因于显著改善的体内稳定性。Ga-68-cybridde可以灵敏地检测原位小鼠模型中的胰腺癌病变，并且在所有健康志愿者中耐受良好。胰腺癌患者的初步PET/CT成像表明，在诊断成像和术后肿瘤复发监测方面，Ga-68-cyberide与F-18-FDG相当。结论：68 Ga-CyClide是一种整合素α（v）β（6）特异性PET放射性示踪剂，具有良好的药代动力学和剂量学特征。Ga-68-cysteide有望为胰腺癌病变检测和治疗反应监测提供一种有效的非侵入性PET策略。
The overexpression of integrin alpha(v)beta(6) in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin alpha(v)beta(6)-targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a Ga-68-labeled integrin alpha(v)beta(6)-targeting cyclic peptide (Ga-68-cycratide) for PET imaging of pancreatic cancer. Methods: Ga-68-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (Ga-68-linear-pep) in an integrin alpha(v)beta(6)-positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (2 women and 3 men) underwent whole-body PET/CT imaging after injection of Ga-68-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of 68Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: Ga-68-cycratide exhibited significantly higher tumor uptake than did Ga-68-linear-pep in BxPC-3 tumor-bearing mice, owing-at least in part-to markedly improved in vivo stability. Ga-68-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that Ga-68-cycratide was comparable to F-18-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin alpha(v)beta(6)-specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. Ga-68-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.