Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
10.1016/j.apsb.2024.05.022
- Author:
Wei GUO
1
;
Xuejun WEN
2
;
Yuhang CHEN
3
;
Tianzhi ZHAO
4
;
Jia LIU
2
;
Yucen TAO
4
;
Hao FU
1
;
Hongjian WANG
3
;
Weizhi XU
1
;
Yizhen PANG
1
;
Liang ZHAO
1
;
Jingxiong HUANG
1
;
Pengfei XU
4
;
Zhide GUO
2
;
Weibing MIAO
5
;
Jingjing ZHANG
4
;
Xiaoyuan CHEN
4
;
Haojun CHEN
1
Author Information
1. Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
3. School of Clinical Medicine, Fujian Medical University, Fuzhou 350005, China.
4. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 138667, Singapore.
5. Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
- Publication Type:Journal Article
- Keywords:
177Lu-LNC1010;
Evans blue;
First-in-human dose escalation study;
Neuroendocrine tumor;
Peptide receptor radionuclide therapy;
Radiolabeled somatostatin analog
- From:
Acta Pharmaceutica Sinica B
2025;15(2):707-721
- CountryChina
- Language:English
-
Abstract:
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.
