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, At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 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 ([At]At-NpGT, [I]I-NpGT, and [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 [At]At-NpGT and [F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice.

Conclusions: [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 [F]F-NpGT and [I]I-NpGT for diagnostic applications and [At]At-NpGT and [I]I-NpGT for therapeutic applications are promising.