文章基本信息

标题：Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy
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作者：Miho Aoki ; Songji Zhao ; Kazuhiro Takahashi 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2020
卷号：68
期号：6
页码：538-545
DOI：10.1248/cpb.c20-00077
出版社：The Pharmaceutical Society of Japan
摘要：There are various diagnostic and therapeutic agents for prostate cancer using bombesin (BBN) derivatives, but astatine-211 ( 211 At)-labeled BBN derivatives have yet to be studied. This study presented a preliminary evaluation of 211 At-labeled BBN derivative. Several nonradioactive iodine-introduced BBN derivatives (IB-BBNs) with different linkers were synthesized and their binding affinities measured. Because IB- 3 exhibited a comparable affinity to native BBN, [ 211 At]AB- 3 was synthesized and the radiochemical yields of [ 211 At]AB- 3 was 28.2 ± 2.4%, with a radiochemical purity of >90%. The stability studies and cell internalization/externalization experiments were performed. [ 211 At]AB- 3 was taken up by cells and internalized; however, radioactivity effluxed from cells over time. In addition, the biodistribution of [ 211 At]AB- 3 , with and without excess amounts of BBN, were evaluated in PC-3 tumor-bearing mice. Despite poor stability in murine plasma, [ 211 At]AB- 3 accumulated in tumor tissue (4.05 ± 0.73%ID/g) in PC-3 tumor-bearing mice, which was inhibited by excess native BBN (2.56 ± 0.24%ID/g). Accumulated radioactivity in various organs is probably due to free 211 At. Peptide degradation in murine plasma and radioactivity efflux from cells are areas of improvement. The development of 211 At-labeled BBN derivatives requires modifying the BBN sequence and preventing deastatination.
关键词：astatine-211;targeted alpha therapy;prostate cancer;bombesin