放射性核素治疗
神经内分泌肿瘤
肽受体
生长抑素受体
医学
剂量学
生长抑素
癌症研究
肿瘤科
药理学
受体
内科学
核医学
作者
Lanlin Yao,Xuejun Wen,Yuhang Chen,Tianzhi Zhao,Jia Liu,Yucen Tao,Hao Fu,Hongjian Wang,Weizhi Xu,Yizhen Pang,Liang Zhao,Jinxiong Huang,Peng‐Fei Xu,Zhide Guo,Weibing Miao,Jingjing Zhang,Xiaoyuan Chen,Haojun Chen
标识
DOI:10.1016/j.apsb.2024.05.022
摘要
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
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