99mTc 标记的 WL12 肽作为肿瘤 PD-L1 靶向 SPECT 成像剂的应用:试剂盒配方、临床前评价和配体影响研究

Pharmaceuticals Pub Date : 2024-07-08 DOI:10.3390/ph17070906
Mingxuan Fan, J. Yao, Zuoquan Zhao, Xianzhong Zhang, Jie Lu
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引用次数: 0

摘要

随着PD-1/PD-L1免疫检查点抑制剂疗法的发展,监测肿瘤微环境中PD-L1表达的能力对于指导治疗非常重要。本研究旨在开发一种具有最佳药代动力学特性的新型放射性示踪剂,通过单光子发射计算机断层扫描(SPECT)成像来反映体内PD-L1的表达。本研究通过试剂盒制备工艺制备了[99mTc]Tc-HYNIC-WL12-tricine/M(M = TPPTS、PDA、ISONIC、4-PSA)复合物,这些复合物具有较高的放射化学纯度(>97%)和合适的摩尔活性(从 100.5 GBq/μmol 到 300 GBq/μmol)。所有 99mTc 标记的 HYNIC-WL12 放射性racer 在体外 4 小时内均表现出良好的稳定性。生物分布研究结果表明,99m锝-HYNIC-共轭放射性racers的药代动力学受放射性racers的连接体影响很大。其中,[99mTc]Tc-HYNIC-WL12-tricine/ISONIC 表现出最佳的药代动力学特性(t1/2α = 8.55 分钟,t1/2β = 54.05 分钟),包括在非目标组织中清除最快、肿瘤与背景对比度最高(例如,肿瘤与肌肉比值、肿瘤与组织比值、肿瘤与组织比值、肿瘤与组织比值)、肿瘤与组织比值最高(例如,肿瘤与组织比值、肿瘤与组织比值、肿瘤与组织比值)、肿瘤与肌肉比值、肿瘤与血液比值分别为:40.42 ± 1.59、14.72 ± 2.77(4 h p.i.),估计辐射吸收剂量最低,凸显了其作为临床 SPECT 成像探针检测肿瘤 PD-L1 的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Application of 99mTc-Labeled WL12 Peptides as a Tumor PD-L1-Targeted SPECT Imaging Agent: Kit Formulation, Preclinical Evaluation, and Study on the Influence of Coligands
With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/μmol to 300 GBq/μmol) were prepared through a kit preparation process. All 99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the 99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t1/2α = 8.55 min, t1/2β = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection.
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