Xiang Qiying, Li Danni, Cheng Chao, Xu Kai, Zuo Changjing
School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China.
Department of Nuclear Medicine, The First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai 200433, China.
Pharmaceuticals (Basel). 2023 Jan 5;16(1):80. doi: 10.3390/ph16010080.
Positron emission tomography (PET) has been proven as an important technology to detect the expression of programmed death ligand 1 (PD-L1) non-invasively and in real time. As a PD-L1 inhibitor, small peptide WL12 has shown great potential in serving as a targeting molecule to guide PD-L1 blockade therapy in clinic. In this study, WL12 was modified with HBED-CC to label Ga in a modified procedure, and the biologic properties were evaluated in vitro and in vivo. Ga-HBED-CC-WL12 showed good stability in saline and can specifically target PD-L1-positive cells U87MG and PANC02. In PANC02-bearing mice, Ga-HBED-CC-WL12 showed fast permeation in subcutaneous tumors within 20 min (SUV 0.37) and was of higher uptake in 90 min (SUV 0.38). When compared with 18F-FDG, Ga-FAPI-04, and Ga-RGD, Ga-HBED-CC-WL12 also demonstrated great image quality and advantages in evaluating immune microenvironment. This study modified the Ga-labeling procedure of WL12 and obtained better biologic properties and further manifested the clinical potential of Ga-HBED-CC-WL12 for PET imaging and guiding for immunotherapy.
正电子发射断层扫描（PET）已被证明是一种重要技术，可用于无创且实时地检测程序性死亡配体1（PD-L1）的表达。作为一种PD-L1抑制剂，小肽WL12在作为靶向分子以指导临床PD-L1阻断治疗方面显示出巨大潜力。在本研究中，WL12用HBED-CC进行修饰以在改进的程序中标记镓，并在体外和体内评估其生物学特性。Ga-HBED-CC-WL12在盐水中显示出良好的稳定性，并且可以特异性靶向PD-L1阳性细胞U87MG和PANC02。在荷PANC02小鼠中，Ga-HBED-CC-WL12在20分钟内显示出在皮下肿瘤中的快速渗透（SUV 0.37），并在90分钟时具有更高的摄取（SUV 0.38）。与18F-FDG、Ga-FAPI-04和Ga-RGD相比，Ga-HBED-CC-WL12在评估免疫微环境方面也表现出优异的图像质量和优势。本研究改进了WL12的镓标记程序并获得了更好的生物学特性，并进一步证明了Ga-HBED-CC-WL12在PET成像和指导免疫治疗方面的临床潜力。
