Gong Jiali, Zhao Lingzhou, Yang Jiqin, Zhu Meilin, Zhao Jinhua
Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Pharmaceutics. 2022 May 6;14(5):996. doi: 10.3390/pharmaceutics14050996.
Certain receptors are often overexpressed during tumor occurrence and development and closely correlate with carcinogenesis. Owing to its overexpression on the cell membrane and cytoplasm of various tumors, plectin, which is involved in tumor proliferation, migration, and invasion, has been viewed as a promising target for cancer imaging. Hence, plectin-targeting agents have great potential as imaging probes for tumor diagnosis. In this study, we developed a [Tc]Tc-labeled plectin-targeted peptide (PTP) as a novel single-photon emission computed tomography (SPECT) probe for tumor imaging and investigated its pharmacokinetics, biodistribution, and targeting ability in several types of tumor-bearing mouse models. The PTP had good biocompatibility and targeting ability to tumor cells in vitro and could be readily labeled with [Tc]Tc after modification with the bifunctional chelator 6-hydrazino nicotinamide (HYNIC). Furthermore, the prepared [Tc]Tc-labeled PTP ([Tc]Tc-HYNIC-PTP) showed high radiochemical purity and excellent stability in vitro. In addition, favorable biodistribution, fast blood clearance, and clear accumulation of [Tc]Tc-HYNIC-PTP in several types of tumors were observed, with a good correlation between tumor uptake and plectin expression levels. These results indicate the potential of [Tc]Tc-HYNIC-PTP as a novel SPECT probe for tumor imaging.
某些受体在肿瘤发生和发展过程中常常过度表达，且与致癌作用密切相关。由于网蛋白（plectin）在各种肿瘤的细胞膜和细胞质上过度表达，参与肿瘤增殖、迁移和侵袭，因此被视为癌症成像的一个有前景的靶点。因此，靶向网蛋白的试剂作为肿瘤诊断的成像探针具有巨大潜力。在本研究中，我们开发了一种[锝（Tc）]Tc标记的靶向网蛋白的肽（PTP）作为一种新型的用于肿瘤成像的单光子发射计算机断层扫描（SPECT）探针，并研究了其在几种荷瘤小鼠模型中的药代动力学、生物分布和靶向能力。PTP在体外具有良好的生物相容性和对肿瘤细胞的靶向能力，在用双功能螯合剂6-肼基烟酰胺（HYNIC）修饰后可以很容易地用[锝（Tc）]Tc标记。此外，制备的[锝（Tc）]Tc标记的PTP（[锝（Tc）]Tc-HYNIC-PTP）在体外显示出高放射化学纯度和优异的稳定性。另外，观察到[锝（Tc）]Tc-HYNIC-PTP在几种肿瘤中具有良好的生物分布、快速的血液清除和明显的蓄积，肿瘤摄取与网蛋白表达水平之间具有良好的相关性。这些结果表明[锝（Tc）]Tc-HYNIC-PTP作为一种新型的用于肿瘤成像的SPECT探针具有潜力。
