Guizhou University Medicine College, Guiyang 550025, Guizhou Province, China.
Key Laboratory of Carcinogenesis and Translational Research (ministry of Education/Beijing), key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration) of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Mol Pharm. 2022 Nov 7;19(11):4149-4156. doi: 10.1021/acs.molpharmaceut.2c00541. Epub 2022 Oct 5.
Angiotensin-converting enzyme 2 (ACE2) is closely related to tumor formation. We developed the radiolabeled peptide pair Ga/Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated DX600 (Ga/Lu-HZ20), for the targeting and mapping of ACE2-overexpressing tumors. Ga/Lu-HZ20 was prepared with a routine labeling method. HepG2/HepG2 cell lines were used to evaluate the specificity of Ga/Lu-HZ20. Pharmacokinetics, biodistribution, and micro-PET/CT and -SPECT/CT imaging were performed, and radiation dosimetry was estimated. Immunohistochemistry (IHC) staining was performed to assess the expression of ACE2 in tumors. The radiolabeling yields of Ga/Lu-HZ20 were 88.49 ± 8.57% ( > 10) and 84.71 ± 9.75% ( > 10), with specific activities of (18.74 ± 3.72) × 10 and (17.85 ± 1.62) × 10 GBq/mol, respectively. Ga/Lu-HZ20 showed significant differences in the cellular uptake of HepG2/HepG2 cells and fast clearance in KM mice. Moreover, HepG2 tumors were clearly visualized in Ga/Lu-HZ20 micro-PET/SPECT images. Based on micro-PET/CT, the standard uptake value (SUVmax) of HepG2 tumors was 0.66 ± 0.02 at 30 min postinjection, IHC confirmed the high expression of ACE2 in HepG2 tumors. In PET/CT images, the SUVmean of volunteer 1 was higher than the F-FDG value in the same lesion. Ga/Lu-HZ20 was successfully obtained and showed high and specific uptake in tumors overexpressing ACE2. They may serve as paired probes for ACE2-targeting theranostics.
血管紧张素转化酶 2（ACE2）与肿瘤的形成密切相关。我们开发了放射性标记的肽对镓/镥标记的 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）-缀合的 DX600（Ga/Lu-HZ20），用于靶向和绘制 ACE2 过表达肿瘤。Ga/Lu-HZ20 通过常规标记方法制备。使用 HepG2/HepG2 细胞系评估 Ga/Lu-HZ20 的特异性。进行药代动力学、生物分布、micro-PET/CT 和 -SPECT/CT 成像以及辐射剂量估计。进行免疫组织化学（IHC）染色以评估肿瘤中 ACE2 的表达。Ga/Lu-HZ20 的放射性标记产率分别为 88.49 ± 8.57%（>10）和 84.71 ± 9.75%（>10），比活度分别为（18.74 ± 3.72）×10 和（17.85 ± 1.62）×10 GBq/mol。Ga/Lu-HZ20 在 HepG2/HepG2 细胞的细胞摄取方面表现出显著差异，并且在 KM 小鼠中快速清除。此外，Ga/Lu-HZ20 可清楚地显示在 HepG2 肿瘤的 micro-PET/SPECT 图像中。基于 micro-PET/CT，HepG2 肿瘤的标准摄取值（SUVmax）在注射后 30 分钟时为 0.66 ± 0.02，IHC 证实 HepG2 肿瘤中 ACE2 的高表达。在 PET/CT 图像中，志愿者 1 的 SUVmean 高于同一病变中 F-FDG 的值。成功获得了 Ga/Lu-HZ20，并且在 ACE2 过表达的肿瘤中表现出高特异性摄取。它们可能作为 ACE2 靶向治疗的配对探针。
