α-Emitting cancer therapy using 211 At-AAMT targeting LAT1

Abstract

α-Methyl-l-tyrosine (AMT) has a high affinity for the cancer-specific l-type amino acid transporter 1 (LAT1). Therefore, we established an anti-cancer therapy, with ²¹¹ At-labeled α-methyl-l-tyrosine (²¹¹ At-AAMT) as a carrier of ²¹¹ At into tumors. ²¹¹ At-AAMT had high affinity for LAT1, inhibited tumor cell growth, and induced DNA double-stranded breaks in vitro. We evaluated the accumulation of ²¹¹ At-AAMT in vivo and the role of LAT1. Treatment with 0.4 MBq/mouse ²¹¹ At-AAMT inhibited tumor growth in the PANC-1 tumor model and 1 MBq/mouse ²¹¹ At-AAMT inhibited metastasis in the lung of the B16F10 metastasis model. Our results suggested that ²¹¹ At would be useful for anti-cancer therapy and that LAT1 is suitable as a target for radionuclide therapy.

Keywords: amino acid; anti-cancer drug; astatine-211; large neutral amino acid transporter 1; nuclear medicine.