2025-12-08 京都大学
<関連情報>
- https://www.kyoto-u.ac.jp/ja/research-news/2025-12-08
- https://www.kyoto-u.ac.jp/sites/default/files/2025-12/WEB_2512_Temma-8756bfd6d238df4e2e830a95127b7de1.pdf
- https://link.springer.com/article/10.1007/s00259-025-07668-3
LAT1選択性PETトレーサーである5-[¹⁸F]F-αMe-3BPAは、ホウ素中性子捕捉療法における構造的に一致する¹⁰B類似体の補助として使用される A LAT1-selective PET tracer, 5-[¹⁸F]F-αMe-3BPA, as a companion to its structurally matched ¹⁰B analog in boron neutron capture therapy
Naoya Kondo,Fuko Hirano,Yasukazu Kanai,Kensuke Suzuki,Anna Miyazaki & Takashi Temma
European Journal of Nuclear Medicine and Molecular Imaging Published:18 November 2025
DOI:https://doi.org/10.1007/s00259-025-07668-3
Abstract
Purpose
This study aimed to develop and evaluate 5-[¹⁸F]F-αMe-3BPA, a novel PET probe designed as a theranostic partner for 5F-αMe-3[¹⁰B]BPA in Boron Neutron Capture Therapy (BNCT). The goal was to address limitations of the clinically used BPA/[¹⁸F]FBPA pair, including poor water solubility, limited LAT1 specificity, and suboptimal diagnostic performance, thereby improving tumor-selective drug delivery and enabling accurate prediction of therapeutic biodistribution through structure-matched PET/BNCT.
Methods
LAT1 dependency was tested in vitro using cancer cell lines with differential LAT1 expression. In vivo biodistribution of both therapeutic agents and their ¹⁸F-labeled analogs were assessed in xenograft mouse models. Radiosynthesis of 5-[¹⁸F]F-αMe-3BPA was achieved via copper-catalyzed nucleophilic radiofluorination. PET/CT imaging compared tumor visualization with [¹⁸F]FBPA. Co-injection studies (5-[¹⁸F]F-αMe-3BPA/5F-αMe-3BPA and [¹⁸F]FBPA/BPA) quantitatively evaluated concordance between ¹⁸F radioactivity and boron concentrations across tissues.
Results
5F-αMe-3BPA uptake in cancer cells was strictly LAT1-dependent. In LAT1-high T3M-4 xenografts, its tumor-to-muscle boron ratio (22) far exceeded BPA (3.4). 5-[¹⁸F]F-αMe-3BPA was synthesized successfully and achieved a tumor-to-muscle ratio of 29 versus 5.3 for [¹⁸F]FBPA. PET imaging showed clear, high-contrast visualization of T3M-4 tumors, with co-injection confirming strong concordance between PET probe and therapeutic agent biodistribution.
Conclusion
The 5-[¹⁸F]F-αMe-3BPA/5F-αMe-3[¹⁰B]BPA theranostic pair demonstrates high LAT1 specificity, low normal tissue uptake, and strong pharmacokinetic alignment, enabling accurate prediction of therapeutic boron delivery for BNCT. Furthermore, 5-[¹⁸F]F-αMe-3BPA shows promise as a dedicated LAT1 imaging probe for advancing LAT1-targeted therapies.
