{"title":"Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics","authors":"Yuta Kaizuka, Hiroyuki Suzuki, Tadashi Watabe, Kazuhiro Ooe, Atsushi Toyoshima, Kazuhiro Takahashi, Koichi Sawada, Takashi Iimori, Yoshitada Masuda, Takashi Uno, Kento Kannaka, Tomoya Uehara","doi":"10.1186/s41181-024-00244-4","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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, <sup>211</sup>At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use <sup>211</sup>At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed.</p><h3>Results</h3><p>We designed and synthesized new radiohalogen-labeled amino acid derivatives ([<sup>211</sup>At]At-NpGT, [<sup>125</sup>I]I-NpGT, and [<sup>18</sup>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 [<sup>211</sup>At]At-NpGT and [<sup>18</sup>F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [<sup>211</sup>At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice.</p><h3>Conclusions</h3><p>[<sup>211</sup>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 [<sup>18</sup>F]F-NpGT and [<sup>123/131</sup>I]I-NpGT for diagnostic applications and [<sup>211</sup>At]At-NpGT and [<sup>131</sup>I]I-NpGT for therapeutic applications are promising.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00244-4","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Radiopharmacy and Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s41181-024-00244-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
Abstract
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, 211At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211At 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 ([211At]At-NpGT, [125I]I-NpGT, and [18F]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 [211At]At-NpGT and [18F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice.
Conclusions
[211At]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 [18F]F-NpGT and [123/131I]I-NpGT for diagnostic applications and [211At]At-NpGT and [131I]I-NpGT for therapeutic applications are promising.