Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, 4221 Xiang'An South Rd, Xiamen 361102, China.
Mol Pharm. 2022 Sep 5;19(9):3178-3186. doi: 10.1021/acs.molpharmaceut.2c00270. Epub 2022 Aug 16.
Currently, the 5-year survival rate for patients with advanced hepatocellular carcinoma (HCC) is very low. Therefore, there is an urgent need to find new strategies for the treatment of HCC. TMTP1 (NVVRQ) is a tumor-homing peptide that has been shown to target a range of highly metastatic tumor cells. In this study, a novel radiotherapeutic probe, [Lu]Lu-DOTA-EB-TMTP1, was synthesized and used to explore the antitumor efficacy in an HCC tumor model. The albumin-binding TMTP1 radioligand was achieved with >98% radiochemical purity. Long tumor retention property of [Lu]Lu-DOTA-EB-TMTP1 was exhibited in single photon emission computed tomography (SPECT) imaging and biodistribution study. The [Lu]Lu-DOTA-EB-TMTP1 showed significant accumulation in the SMMC-7721 HCC tumor with an uptake value of 9.67 ± 1.27 %ID/g at 8 h and a T/M ratio of 6.4. In radiotherapy studies, 30 days after injection of [Lu]Lu-DOTA-EB-TMTP1, the tumor inhibition rate reached 93.2 ± 0.10 and 94.9 ± 0.04% in the 18.5 and 29.6 MBq high-dose groups, respectively. These preclinical data suggest that [Lu]Lu-DOTA-EB-TMTP1 may be an effective treatment option for HCC and should be further evaluated in human trials.
目前，晚期肝细胞癌 (HCC) 患者的 5 年生存率非常低。因此，迫切需要寻找治疗 HCC 的新策略。TMTP1 (NVVRQ) 是一种肿瘤归巢肽，已被证明可靶向多种高转移性肿瘤细胞。在这项研究中，合成了一种新型放射治疗探针 [Lu]Lu-DOTA-EB-TMTP1，并用于研究 HCC 肿瘤模型中的抗肿瘤疗效。白蛋白结合 TMTP1 放射性配体的放射化学纯度 >98%。单光子发射计算机断层扫描 (SPECT) 成像和生物分布研究显示，[Lu]Lu-DOTA-EB-TMTP1 具有较长的肿瘤滞留特性。[Lu]Lu-DOTA-EB-TMTP1 在 SMMC-7721 HCC 肿瘤中有明显的积聚，在 8 小时时摄取值为 9.67±1.27%ID/g，T/M 比值为 6.4。在放射治疗研究中，在注射 [Lu]Lu-DOTA-EB-TMTP1 30 天后，18.5 和 29.6 MBq 高剂量组的肿瘤抑制率分别达到 93.2±0.10%和 94.9±0.04%。这些临床前数据表明，[Lu]Lu-DOTA-EB-TMTP1 可能是治疗 HCC 的有效治疗选择，应在人体试验中进一步评估。
