体内分布
肽
化学
癌症研究
体内
免疫组织化学
免疫疗法
免疫系统
临床前影像学
荧光寿命成像显微镜
分子成像
免疫检查点
单克隆抗体
显像剂
蛋白质表达
分子生物学
荧光
体外
正电子发射断层摄影术
肿瘤细胞
Pet成像
肽库
细胞培养
抗体
作者
Xiuting Lin,Jiayu Fu,Linping Fu,Jie Zang,Weibing Miao,Zihua Wang
标识
DOI:10.1021/acs.molpharmaceut.5c01194
摘要
Programmed death-ligand 1 (PD-L1) is a key immune checkpoint protein that facilitates tumor immune escape and correlates with response to immune checkpoint inhibitor therapy. However, noninvasive, real-time assessment of dynamic PD-L1 expression remains challenging due to tumor heterogeneity and limitations of tissue biopsies. In this study, we rationally designed and evaluated a novel 68Ga-labeled peptide-based radiotracer, 68Ga-DOTA-P6, for PET imaging of PD-L1. The PD-L1-targeting peptide P6 was identified via a high-throughput OBOC peptide library and validated using SPR and cellular fluorescence assays. The radiotracer demonstrated high radiochemical purity (>95%) and excellent stability in saline, PBS, and fetal bovine serum (>90% intact after 2 h). In vivo micro-PET/CT imaging in H1975 and MDA-MB-231 tumor-bearing mice revealed rapid, PD-L1-dependent tumor accumulation. Co-injection of unlabeled P6 reduced tumor uptake by 69%, confirming specificity. Biodistribution studies showed highest accumulation in kidneys and significant tumor uptake. Immunohistochemistry confirmed PD-L1 overexpression in H1975 tumors, with a strong correlation between SUVmax and PD-L1 levels (r = 0.8060, p < 0.001). Together, these findings demonstrate the promise of 68Ga-DOTA-P6 for noninvasive imaging of PD-L1 expression and potential prediction of immunotherapy response.
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