新型 PD-L1 靶向 PET 探针[F]AlF-PAI-PDL1p 和[Ga]Ga-PAI-PDL1p 的对比研究及其在肿瘤成像中的应用。
Comparative study of [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p as novel PD-L1 targeting PET probes for tumor imaging.
机构信息
GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Guangdong Provincial Key Laboratory of New Drug Screening, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
出版信息
Bioorg Chem. 2024 Oct;151:107660. doi: 10.1016/j.bioorg.2024.107660. Epub 2024 Jul 25.
PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [F]AlF-PAI-PDL1p and [Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.
PD-L1 在许多肿瘤中表达，但在正常组织中很少表达，因此它可以成为 PET 成像的靶标。在这项工作中，我们开发了新的基于肽的 PET 探针 [F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p，产率分别为 20-25%和 40-55%。[F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p 在 30 分钟内合成，具有高摩尔活性。[F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p 在体内和体外表现出良好的稳定性。体外细胞研究表明 [F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p 特异性靶向 PD-L1，在 60 分钟时在 B16F10 细胞中的摄取率分别为 61.52±4.39%ID/100 万个细胞和 19.29±2.17%ID/100 万个细胞。生物分布结果表明，[F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p 肝脏积累均较低。体内 PET 成像结果表明，[F]AlF-PAI-PDL1p 在 2 小时时具有较高的肿瘤摄取率，为 4.23±0.81%ID/g，在 12 小时时摄取率增加至 6.60±1.01%ID/g。[Ga]Ga-PAI-PDL1p 在 2 小时时也显示出较高的肿瘤摄取率，为 2.30±0.20%ID/g，在 6 小时时摄取率略有增加，为 3.80±0.26%ID/g。总之，[F]AlF-PAI-PDL1p 和 [Ga]Ga-PAI-PDL1p 似乎是 PD-L1 表达 PET 成像的潜在示踪剂。
Zotero 插件