Background Adnectin is a protein family derived from the 10th type III domain of human fibronectin ((10)Fn3) with high-affinity targeting capabilities. Positron emission tomography (PET) probes derived from anti-programmed death ligand-1 (PD-L1) Adnectins, including F-18- and Ga-68-labeled BMS-986192, are recently developed for the prediction of patient response to immune checkpoint blockade. The Ga-68-labeled BMS-986192, in particular, is an attractive probe for under-developed regions due to the broader availability of Ga-68. However, the pharmacokinetics and biocompatibility of Ga-68-labeled BMS-986192 are still unknown, especially in non-human primates, impeding its further clinical translation. Methods We developed a variant of Ga-68-labeled BMS-986192 using 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) as the radionuclide-chelator. The resultant probe, Ga-68-NODAGA-BMS986192, was evaluated in terms of targeting specificity using a bilateral mouse tumor model inoculated with wild-type B16F10 and B16F10 transduced with human PD-L1 (hPD-L1-B16F10). The dynamic biodistribution and radiation dosimetry of this probe were also investigated in non-human primate cynomolgus. Results Ga-68-NODAGA-BMS986192 was prepared with a radiochemical purity above 99%. PET imaging with Ga-68-NODAGA-BMS986192 efficiently delineated the hPD-L1-B16F10 tumor at 1 h post-injection. The PD-L1-targeting capability of this probe was further confirmed using in vivo blocking assay and ex vivo biodistribution studies. PET dynamic imaging in both mouse and cynomolgus models revealed a rapid clearance of the probe via the renal route, which corresponded to the low background signals of the PET images. The probe also exhibited a favorable radiation dosimetry profile with a total-body effective dose of 6.34E-03 mSv/MBq in male cynomolgus. Conclusions Ga-68-NODAGA-BMS986192 was a feasible and safe tool for the visualization of human PD-L1. Our study also provided valuable information on the potential of targeted PET imaging using Adnectin-based probes.
基金：
National Natural Science Foundation of China [91959119, 81873903, 81671718]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Nucl Med, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Zhou Huimin,Bao Guangfa,Wang Ziqiang,et al.PET imaging of an optimized anti-PD-L1 probe 68Ga-NODAGA-BMS986192 in immunocompetent mice and non-human primates[J].EJNMMI RESEARCH.2022,12(1):doi:10.1186/s13550-022-00906-x.
APA：
Zhou, Huimin,Bao, Guangfa,Wang, Ziqiang,Zhang, Buchuan,Li, Dan...&Zhu, Xiaohua.(2022).PET imaging of an optimized anti-PD-L1 probe 68Ga-NODAGA-BMS986192 in immunocompetent mice and non-human primates.EJNMMI RESEARCH,12,(1)
MLA：
Zhou, Huimin,et al."PET imaging of an optimized anti-PD-L1 probe 68Ga-NODAGA-BMS986192 in immunocompetent mice and non-human primates".EJNMMI RESEARCH 12..1(2022)
