Preliminary Evaluation of Astatine-211-Labeled Bombesin Derivatives for Targeted Alpha Therapy
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- Aoki Miho
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University Graduate School of Medical Sciences, Kanazawa University
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- Zhao Songji
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Takahashi Kazuhiro
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Washiyama Kohshin
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Ukon Naoyuki
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Tan Chengbo
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Shimoyama Saki
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Nishijima Ken-ichi
- Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University
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- Ogawa Kazuma
- Graduate School of Medical Sciences, Kanazawa University Institute for Frontier Science Initiative, Kanazawa University
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Abstract
<p>There are various diagnostic and therapeutic agents for prostate cancer using bombesin (BBN) derivatives, but astatine-211 (211At)-labeled BBN derivatives have yet to be studied. This study presented a preliminary evaluation of 211At-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, [211At]AB-3 was synthesized and the radiochemical yields of [211At]AB-3 was 28.2 ± 2.4%, with a radiochemical purity of >90%. The stability studies and cell internalization/externalization experiments were performed. [211At]AB-3 was taken up by cells and internalized; however, radioactivity effluxed from cells over time. In addition, the biodistribution of [211At]AB-3, with and without excess amounts of BBN, were evaluated in PC-3 tumor-bearing mice. Despite poor stability in murine plasma, [211At]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 211At. Peptide degradation in murine plasma and radioactivity efflux from cells are areas of improvement. The development of 211At-labeled BBN derivatives requires modifying the BBN sequence and preventing deastatination.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 68 (6), 538-545, 2020-06-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390848250114622976
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- NII Article ID
- 130007850061
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- NII Book ID
- AA00602100
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 030429660
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- PubMed
- 32475858
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed