Development of LAT1-Selective Nuclear Medicine Therapeutics Using Astatine-211.

Autor: Kaneda-Nakashima K; Radiation Biological Chemistry, MS-CORE, FRC, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Shirakami Y; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Hisada K; Radiation Biological Chemistry, MS-CORE, FRC, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan., Feng S; Radiation Biological Chemistry, MS-CORE, FRC, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan., Kadonaga Y; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Ooe K; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Watabe T; Department of Radiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan., Manabe Y; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan.; Natural Product Chemistry, Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan., Shimoyama A; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan.; Natural Product Chemistry, Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan., Murakami M; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Toyoshima A; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan., Haba H; Nishina Center, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan., Kanai Y; Premium Research Institute for Human Metaverse Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan., Fukase K; Institute for Radiation Sciences, Osaka University, 2-4 Yamadaoka, Suita, Osaka 565-0871, Japan.; Natural Product Chemistry, Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Nov 18; Vol. 25 (22). Date of Electronic Publication: 2024 Nov 18.
DOI: 10.3390/ijms252212386
Abstrakt: We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 ( 211 At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[ 211 At] Astato-α-methyl-L-tyrosine ( 211 At-AAMT-OH-L). We used a unique labeling method. By changing the OH group of phenol to a methyl group, retention was successfully increased. It was also found that the amount of the L-isomer taken up by the D-isomer and L-isomer was clearly higher, and the L-isomer was superior as a therapeutic drug. Compounds in which the methyl group was replaced with an ethyl or propyl group were also examined, but their retention did not increase significantly. In fact, we observed increased non-specific accumulation and dynamics, suggesting that labeling may be off. In addition, 211 At-AAMT-O-Me-L, which has a simple structure, was clearly superior in terms of uptake speed for several candidate compounds. As a result, we were able to develop a compound that can be easily labeled, has high specific radioactivity, is stable, and has a strong therapeutic effect.
Databáze: MEDLINE
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