Recently, we selected a novel anti-hPD-L1-specific HCAb named Nb6 with high affinity (EC50 = 0.65 ng/mL) for potential hPD-L1 targeted non-invasive PET imaging. In this research, Nb6 was conjugated with the bifunctional chelator NCS-Bz-NOTA ((2-[(4-Isothiocyanophenyl) methyl]-1,4,7-triazacy-clononane-1,4,7-triacetic acid)) and further labeled with radio-nuclide 64Cu. 64Cu-NOTA-Nb6 was prepared with over 95% labeling yield, over 99% radiochemical purity and 14-16 GBq/μmol specific activity after PD-10 column purification. It shows good stability in 0.01 M PBS and 5% HSA solutions. 64Cu-NOTA-Nb6 has a high binding affinity to 3.60 nM which was tested by humanlungadenocarcinoma A549 cell lines. Tumor lesion can be clearly observed from 20 h to 38 h by Micro-PET equipment after 64Cu-NOTA-Nb6 administration. The study revealed that 64Cu-NOTA-Nb6 has good lesion detection ability, high ratios between tumor and non-tumor signal and can specifically target A549 xenografted tumor model. Taken together of good stability, high binding affinity, and tumor detection ability, 64Cu labeled Nb6 is a promising radio-tracer in diagnosing of hPD-L1 overexpression tumor, supposed to monitor PD-L1overexpression tumor progression and guide targeted therapy with PET molecular imaging.

中文翻译：

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评价64Cu放射性标记的抗hPD-L1 Nb6在肺癌肿瘤小鼠模型中的正电子发射断层显像成像。

最近，我们选择了一种具有高亲和力（EC50 = 0.65 ng / mL）的新型抗hPD-L1特异性HCAb Nb6，用于潜在的针对hPD-L1的非侵入性PET成像。在这项研究中，Nb6与双功能螯合剂NCS-Bz-NOTA（（2-[（4-异硫氰基苯基）甲基] -1,4,7-三叠氮基-氯壬烷-1,4,7-三乙酸）共轭和进一步用放射性核素64Cu标记。PD-10色谱柱纯化后，制备的64Cu-NOTA-Nb6的标记收率超过95％，放射化学纯度超过99％，比活性为14-16 GBq /μmol。在0.01 M PBS和5％HSA溶液中显示出良好的稳定性。64Cu-NOTA-Nb6对3.60 nM具有高结合亲和力，这已通过人肺腺癌A549细胞株进行了测试。使用64Cu-NOTA-Nb6后，用Micro-PET设备可在20 h至38 h清楚地观察到肿瘤病变。研究表明64Cu-NOTA-Nb6具有良好的病变检测能力，肿瘤与非肿瘤信号之间的比率较高，并且可以特异性针对A549异种移植肿瘤模型。综合了良好的稳定性，高结合亲和力和肿瘤检测能力，64Cu标记的Nb6是诊断hPD-L1过表达肿瘤的有前途的放射性示踪剂，被认为可以监测PD-L1过表达的肿瘤进展并通过PET分子成像指导靶向治疗。