Research Papers:

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

Tadashi Watabe _, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Yuwei Liu, Kazuhiro Ooe, Takahiro Teramoto, Atsushi Toyoshima, Eku Shimosegawa, Takashi Nakano, Yoshikatsu Kanai, Atsushi Shinohara and Jun Hatazawa

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Oncotarget. 2020; 11:1388-1398. https://doi.org/10.18632/oncotarget.27552

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Tadashi Watabe1,2, Kazuko Kaneda-Nakashima2,3, Yoshifumi Shirakami2, Yuwei Liu1, Kazuhiro Ooe1,2, Takahiro Teramoto2, Atsushi Toyoshima2, Eku Shimosegawa2,4, Takashi Nakano2,5, Yoshikatsu Kanai6, Atsushi Shinohara2,7 and Jun Hatazawa2,5

1 Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Suita, Japan

2 Institute for Radiation Sciences, Osaka University, Suita, Japan

3 Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan

4 Department of Molecular Imaging in Medicine, Graduate School of Medicine, Osaka University, Suita, Japan

5 Research Center for Nuclear Physics, Osaka University, Ibaraki, Japan

6 Department of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Japan

7 Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan

Correspondence to:

Tadashi Watabe,email: [email protected]

Keywords: alpha therapy; astatine; glioma; LAT1; phenylalanine

Received: January 28, 2020     Accepted: March 14, 2020     Published: April 14, 2020


Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine (211At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.

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