Α‐Emitting cancer therapy using 211At‐AAMT targeting LAT1. Issue 3 (22nd January 2021)

• Record Type: Journal Article
• Authors: Kaneda‐Nakashima, Kazuko; Zhang, ZiJian; Manabe, Yoshiyuki; Shimoyama, Atsushi; Kabayama, Kazuya; Watabe, Tadashi; Kanai, Yoshikatsu; Ooe, Kazuhiro; Toyoshima, Atsushi; Shirakami, Yoshifumi; Yoshimura, Takashi; Fukuda, Mitsuhiro; Hatazawa, Jun; Nakano, Takashi; Fukase, Koichi; Shinohara, Atsushi
• Is Part Of: Cancer science. Volume 112:Issue 3(2021)
• Page Start: 1132
• Page End: 1140
• Publication Date: 2021-01-22
• Subjects: amino acid -- anti‐cancer drug -- astatine‐211 -- large neutral amino acid transporter 1 -- nuclear medicine; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14761
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : α‐Methyl‐l ‐tyrosine (AMT) has a high affinity for the cancer‐specific l ‐type amino acid transporter 1 (LAT1). Therefore, we establish an anti‐cancer therapy using 211 At‐labeled α‐methyl‐l ‐tyrosine ( 211 At‐AAMT) as a carrier of 211 At into tumors. 211 At is useful for anti‐cancer therapy and LAT1 was suitable as a target for nuclear medicine.