Division of Science, Institute for Radiation Sciences, Osaka University, Osaka, Japan.
MS-CORE, PRC, Graduate School of Science, Osaka University, Osaka, Japan.
Cancer Sci. 2021 Mar;112(3):1132-1140. doi: 10.1111/cas.14761. Epub 2021 Jan 22.
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 At-labeled α-methyl-l-tyrosine ( At-AAMT) as a carrier of At into tumors. At-AAMT had high affinity for LAT1, inhibited tumor cell growth, and induced DNA double-stranded breaks in vitro. We evaluated the accumulation of At-AAMT in vivo and the role of LAT1. Treatment with 0.4 MBq/mouse At-AAMT inhibited tumor growth in the PANC-1 tumor model and 1 MBq/mouse At-AAMT inhibited metastasis in the lung of the B16F10 metastasis model. Our results suggested that At would be useful for anti-cancer therapy and that LAT1 is suitable as a target for radionuclide therapy.
α-甲基-L-酪氨酸（AMT）对癌症特异性 L 型氨基酸转运蛋白 1（LAT1）具有高亲和力。因此，我们建立了一种抗癌疗法，使用放射性标记的 α-甲基-L-酪氨酸（At-AAMT）作为放射性原子进入肿瘤的载体。At-AAMT 对 LAT1 具有高亲和力，可抑制肿瘤细胞生长，并在体外诱导 DNA 双链断裂。我们评估了 At-AAMT 在体内的积累和 LAT1 的作用。用 0.4MBq/只小鼠的 At-AAMT 治疗可抑制 PANC-1 肿瘤模型中的肿瘤生长，用 1MBq/只小鼠的 At-AAMT 治疗可抑制 B16F10 转移模型中的肺转移。我们的结果表明，放射性原子可用于抗癌治疗，LAT1 适合作为放射性核素治疗的靶点。
