68Ga-labeled ODAP-Urea-based PSMA agents in prostate cancer: first-in-human imaging of an optimized agent

体内分布 尿素 前列腺癌 谷氨酸羧肽酶Ⅱ 配体(生物化学) 化学 药代动力学 体内 放射化学 核医学 核化学 癌症 体外 生物化学 药理学 医学 受体 内科学 生物技术 生物
作者
Xiaojiang Duan,Z. Cao,Hua Zhu,Chen Liu,Xiaojun Zhang,Jinming Zhang,Yanan Ren,Futao Liu,Xuekang Cai,Xiaoyi Guo,Zhen Xi,Martin G. Pomper,Zhi Yang,Yan Fan,Xing Yang
出处
期刊:European Journal of Nuclear Medicine and Molecular Imaging [Springer Science+Business Media]
卷期号:49 (3): 1030-1040 被引量:25
标识
DOI:10.1007/s00259-021-05486-x
摘要

Prostate-specific membrane antigen (PSMA) is a promising target for prostate cancer imaging and therapy. The most commonly used scaffold incorporates a glutamate-urea (Glu-Urea) function. We recently developed oxalyldiaminopropionic acid-urea (ODAP-Urea) PSMA ligands in an attempt to improve upon the pharmacokinetic properties of existing agents. Here, we report the synthesis of an optimized 68Ga-labeled ODAP-Urea-based ligand, [68Ga]Ga-P137, and first-in-human results.Twelve ODAP-Urea-based ligands were synthesized and radiolabeled with 68Ga in high radiochemical yield and purity. Their PSMA inhibitory capacities were determined using the NAALADase assay. Radioligands were evaluated in mice-bearing 22Rv1 prostate tumors by microPET. Lead compound [68Ga]Ga-P137 was evaluated for stability, cell uptake, and biodistribution. PET imaging of [68Ga]Ga-P137 was performed in three patients head-to-head compared to [68Ga]Ga-PSMA-617.Ligands were synthesized in 11.1-44.4% yield and > 95% purity. They have high affinity to PSMA (Ki of 0.13 to 5.47 nM). [68Ga]Ga-P137 was stable and hydrophilic. [68Ga]Ga-P137 showed higher uptake than [68Ga]Ga-PSMA-617 in tumor-bearing mice at 6.43 ± 0.98%IA/g vs 3.41 ± 1.31%IA/g at 60-min post-injection. In human studies, the normal organ biodistribution of [68Ga]Ga-P137 was grossly equivalent to that of [68Ga]Ga-PSMA-617 except for within the urinary tract, in which [68Ga]Ga-P137 demonstrated lower uptake.The optimized ODAP-Urea-based ligand [68Ga]Ga-P137 can image PSMA in xenograft models and humans, with lower bladder accumulation to the Glu-Urea-based agent, [68Ga]Ga-PSMA-617, in a preliminary, first-in-human study.ClinicalTrials.gov Identifier: NCT04560725, Registered 23 September 2020. https://clinicaltrials.gov/ct2/show/NCT04560725.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
lllllcc发布了新的文献求助10
刚刚
cherryhuang发布了新的文献求助10
1秒前
完美世界应助醉熏的玉兰采纳,获得10
4秒前
4秒前
星星发布了新的文献求助10
4秒前
4秒前
慕青应助General采纳,获得10
4秒前
星之芋发布了新的文献求助10
5秒前
Zhang完成签到,获得积分10
5秒前
5秒前
ding发布了新的文献求助10
6秒前
可耐的冰萍完成签到,获得积分10
6秒前
稻草人发布了新的文献求助10
8秒前
ding应助等待的音响采纳,获得10
9秒前
来碗豆腐完成签到 ,获得积分10
9秒前
舒适笑容完成签到,获得积分10
10秒前
Ice发布了新的文献求助10
10秒前
11秒前
11秒前
11秒前
12秒前
pragmatic完成签到,获得积分10
12秒前
13秒前
14秒前
qiao完成签到,获得积分10
14秒前
A拉拉拉发布了新的文献求助10
15秒前
胖头鱼完成签到,获得积分10
17秒前
Joker发布了新的文献求助10
17秒前
俏皮诺言发布了新的文献求助10
17秒前
17秒前
cm发布了新的文献求助30
18秒前
18秒前
呆萌的萝完成签到,获得积分10
18秒前
艺_完成签到 ,获得积分10
19秒前
子衿发布了新的文献求助10
20秒前
20秒前
内向映天完成签到 ,获得积分10
20秒前
羊羊完成签到,获得积分10
21秒前
jpg完成签到,获得积分10
22秒前
研友_8Wzm5Z发布了新的文献求助10
24秒前
高分求助中
Mass producing individuality 600
Разработка метода ускоренного контроля качества электрохромных устройств 500
Chinesen in Europa – Europäer in China: Journalisten, Spione, Studenten 500
Arthur Ewert: A Life for the Comintern 500
China's Relations With Japan 1945-83: The Role of Liao Chengzhi // Kurt Werner Radtke 500
Two Years in Peking 1965-1966: Book 1: Living and Teaching in Mao's China // Reginald Hunt 500
Epigenetic Drug Discovery 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3823927
求助须知:如何正确求助?哪些是违规求助? 3366234
关于积分的说明 10439563
捐赠科研通 3085318
什么是DOI,文献DOI怎么找? 1697342
邀请新用户注册赠送积分活动 816323
科研通“疑难数据库(出版商)”最低求助积分说明 769569