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Establishment of novel targeted alpha-radionuclide medicine

Targeted alpha therapy is receiving much attention in the field of theranostics because of its high cytotoxic effect to the targeting cancer cells. However, physiological uptakes in non-targeted organs are also observed in the targeted alpha therapy, which might lead to the severe side effects. We should consider about both maximizing the treatment effect in the tumor and minimizing the side effects in the organs at risk. From this viewpoint, decision of targeting molecule was most important. We selected LAT1 as molecular target. LAT1 is one of the amino acid transporters. LAT1 has highly specificity to cancer tissues. We developed next-generation internal radiotherapy using chemicals targeting LAT1. First, we synthesized alpha-methyl-L-tylosine labeled with 211 At. 211 At was produced by the cyclotron, and then quickly purified and combined to alpha-methyl-L-tyrosine ( 211 At-AAMT). Next, we performed cytotoxicity evaluation of 211 At-AAMT using PANC-1 cells, Human pancreas cancer cell lines. We also detected the DNA damage by 211 At-AAMT. As a result, cell death and specificity were confirmed in 211 At-AAMT. We also found the anti-cancer effects invivostudy. In the immediate future, we will examine that the effects of 211 At-AAMT using several kinds of tumor-bearing models.