Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics

Background L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, 211 At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211 At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed. Results We designed and synthesized new radiohalogen-labeled amino acid derivatives ([ 211 At]At-NpGT, [ 125 I]I-NpGT, and [ 18 F]F-NpGT) in which L-tyrosine was introduced into the neopentyl glycol (NpG) structure. The radiolabeled amino acid derivatives were recognized as substrates of LAT1 in the in vitro studies using C6 glioma cells. In a biodistribution study using C6 glioma-bearing mice, these agents exhibited high stability against in vivo dehalogenation and similar biodistributions. The similarity of [ 211 At]At-NpGT and [ 18 F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [ 211 At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice. Conclusions [ 211 At]At-NpGT exhibited a dose-dependent inhibitory effect on the tumor growth of glioma-bearing mice, and its biodistribution was similar to that of other radiohalogen-labeled amino acid derivatives. These findings suggest that radiotheranostics using [ 18 F]F-NpGT and [ 123/131 I]I-NpGT for diagnostic applications and [ 211 At]At-NpGT and [ 131 I]I-NpGT for therapeutic applications are promising.