放射性配体
化学
内化
谷氨酸羧肽酶Ⅱ
前列腺癌
体内分布
体内
配体(生物化学)
前列腺
抗原
放射合成
癌症研究
分子生物学
癌症
放射化学
受体
体外
生物化学
内科学
免疫学
医学
生物
生物技术
作者
Vilde Yuli Stenberg,Asta Juzeniene,Qingqi Chen,Xiaoming Yang,Øyvind S. Bruland,Roy H. Larsen
摘要
Prostate‐specific membrane antigen (PSMA) is the most promising target for radioligand therapy of prostate cancer. The aim of this study was to prepare a small molecular ligand p‐SCN‐Bn‐TCMC‐PSMA (NG001) and compare it with the commonly used DOTA‐based PSMA‐617. The PSMA‐targeting ability of the 212 Pb‐labelled ligands was evaluated using PSMA‐positive C4‐2 human prostate cancer cells. Lead‐212 is an in vivo generator of alpha particles by its daughter nuclides 212 Bi and 212 Po. NG001 was synthesized by conjugating the isothiocyanato group of p‐SCN‐Bn‐TCMC to the amino group of a glutamate‐urea‐based PSMA‐binding entity. Molecular size, chelator unit and chelator linking method are different in NG001 and PSMA‐617. Both ligands were efficiently labelled with 212 Pb using a 224 Ra/ 212 Pb‐solution generator in transient equilibrium with progeny. Lead‐212‐labelled NG001 was purified with a yield of 85.9±4.7% and with 0.7±0.2% of 224 Ra. Compared with [ 212 Pb]Pb‐PSMA‐617, [ 212 Pb]Pb‐NG001 displayed a similar binding and internalization in C4‐2 cells, with comparable tumour uptake in mice bearing C4‐2 tumours, but almost a 2.5‐fold lower kidney uptake. Due to the rapid normal tissue clearance and tumour cell internalization, any significant translocalization of 212 Bi was not detected in mice. In conclusion, the obtained results warrant further preclinical studies to evaluate the therapeutic efficacy of [ 212 Pb]Pb‐NG001.
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