@article{oai:repo.qst.go.jp:00080557,
 author = {Oshima, Yasuhiro and Suzuki, Hiroyuki and Hanaoka, Hirofumi and Sasaki, Ichiro and Watanabe, Shigeki and Haba, Hiromitsu and Arano, Yasushi and Tsushima, Yoshito and Ishioka, Noriko and Yasuhiro, Oshima and Ichiro, Sasaki and Shigeki, Watanabe and Noriko, Ishioka},
 journal = {Nuclear Medicine and Biology},
 month = {Nov},
 note = {Targeted α-radionuclide therapy has growing attention as a promising therapy for refractory cancers. However, the application is limited to certain types of cancer. Since L-type amino acid transporter 1 (LAT1) is highly expressed in various human cancers, we prepared LAT1-selective α-emitting amino acid analog, 2-[211At]astato-α-methyl-L-phenylalanine (2-[211At]AAMP), and evaluated its potential as a therapeutic agent. Methods: 2-[211At]AAMP was prepared from the stannyl precursor. Stability of 2-[211At]AAMP was evaluated by both in vitro and in vivo. In vitro studies using LAT1 expressing human ovarian cancer cell line, SKOV3, were performed for evaluating cellular uptake and cytotoxicity of 2-[211At]AAMP. Biodistribution and therapeutic studies in SKOV3 bearing mice were performed after intravenous injection of 2-[211At]AAMP. Results: 2-[211At]AAMP was stable in murine plasma in vitro and excreted into urine as intact. Cellular uptake of 2-[211At]AAMP was inhibited by treatment with LAT1-selective inhibitor. After 24 hours of incubation, 2-[211At]AAMP suppressed clonogenic growth at 10 kBq/ml, and induced cell death and DNA double-strand break at 25 kBq/ml. When injected to mice, 2-[211At]AAMP exhibited the peak accumulation in the tumor at 30 min postinjection, and the radioactivity levels in the tumor retained up to 60 min. The majority of the radioactivity was rapidly eliminated from the body into the urine as an intact form immediately after injection. 2-[211At]AAMP significantly improved the survival of mice (P<0.05) without serious side effects. Conclusion: 2-[211At]AAMP showed α-radiation-dependent cellular growth inhibition after taking up via LAT1. Furthermore, 2-[211At]AAMP provided a beneficial effect on survival in vivo. These findings suggest that 2-[211At]AAMP would be useful for the treatment of LAT1-positive cancer. Advances in Knowledge and Implications for patient Care: This is the first report of LAT1-targeting radiopharmaceutical for α-radionuclide therapy, which would be applicable for the treatment of various types of cancer.},
 pages = {15--22},
 title = {Preclinical evaluation of new α-radionuclide therapy targeting LAT1: 2-[211At]astato-α-methyl-L-phenylalanine in tumor-bearing model},
 volume = {90-91},
 year = {2020}
}