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

Cancer Sci. 2021 Mar;112(3):1132-1140. doi: 10.1111/cas.14761. Epub 2021 Jan 22.

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.

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Astatine / administration & dosage*
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded / radiation effects
  • Disease Models, Animal
  • Drug Carriers / pharmacology*
  • Feasibility Studies
  • Female
  • HEK293 Cells
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Male
  • Mice
  • Neoplasms / pathology
  • Neoplasms / radiotherapy*
  • Xenograft Model Antitumor Assays
  • alpha-Methyltyrosine / pharmacology*

Substances

  • Astatine-211
  • Drug Carriers
  • Large Neutral Amino Acid-Transporter 1
  • SLC7A5 protein, human
  • Slc7a5 protein, mouse
  • alpha-Methyltyrosine
  • Astatine