Hyperthyroidism refers to a clinical state that results from inappropriately hight hyroid hormone levels in the tissues;.Ⅰ-131 therapy plays a critical role and provides a remarkable curative effect in targeting thyr...Hyperthyroidism refers to a clinical state that results from inappropriately hight hyroid hormone levels in the tissues;.Ⅰ-131 therapy plays a critical role and provides a remarkable curative effect in targeting thyroid diseases. Thyroid cells can take up isotope I-131, which emits not only beta rays but also展开更多
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 sh...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^(177)Lu-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^(177)Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain,resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical,^(177)Lu-LNC1010,for PRRT.In preclinical studies,^(177)Lu-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^(177)Lu-LNC1010 in patients with advanced/metastatic NETs.^(177)Lu-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^(177)Lu-EB-TATE.Preliminary PRRT efficacy results showed an 83%disease control rate and a 42%overall response rate after two^(177)Lu-LNC1010 treatment cycles.These encouraging findings warrant further investigations through multicenter,prospective,and randomized controlled trials.展开更多
基金supported by a fund from the Key Project of Natural Science Foundation of Tianjin [16JCZDJC36100]Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences [2017-I2M-1-016]+2 种基金Fundamental Research Funds for the Central Universities [3332018116]PUMC Youth Fund [3332015101]Fundamental Research Funds for CAMS&PUMC [2016ZX310074]
文摘Hyperthyroidism refers to a clinical state that results from inappropriately hight hyroid hormone levels in the tissues;.Ⅰ-131 therapy plays a critical role and provides a remarkable curative effect in targeting thyroid diseases. Thyroid cells can take up isotope I-131, which emits not only beta rays but also
基金supported by the National Natural Science Foundation of China(No.82071961)Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare,Key Scientific Research Program for Yong Scholars in Fujian(No.2021ZQNZD016,China)+5 种基金Fujian Natural Science Foundation for Distinguished Young Scholars(No.2022D005,China)Innovation of Science and Technology,Fujian Province(No.2021Y9134,China)National University of Singapore(No.NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine)National Medical Research Council(No.MOH-001388-00,MOH-001041,CG21APR1005,Singapore)Singapore Ministry of Education(No.MOE-000387-00,Singapore)National Research Foundation(No.NRF-000352-00,Singapore).
文摘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^(177)Lu-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^(177)Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain,resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical,^(177)Lu-LNC1010,for PRRT.In preclinical studies,^(177)Lu-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^(177)Lu-LNC1010 in patients with advanced/metastatic NETs.^(177)Lu-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^(177)Lu-EB-TATE.Preliminary PRRT efficacy results showed an 83%disease control rate and a 42%overall response rate after two^(177)Lu-LNC1010 treatment cycles.These encouraging findings warrant further investigations through multicenter,prospective,and randomized controlled trials.
