Synthesis, in silico and biodistribution studies of a novel 47Sc-radiolabeled α-amino acid ester derivative attached to pyrazine and tetrazole rings for tumor targeted radiotherapy
Mohamed A. Gizawy, Hesham A. Shamsel-Din, Mohsen M. T. El-Tahawy, Ayman A. Ibrahim
{"title":"Synthesis, in silico and biodistribution studies of a novel 47Sc-radiolabeled α-amino acid ester derivative attached to pyrazine and tetrazole rings for tumor targeted radiotherapy","authors":"Mohamed A. Gizawy, Hesham A. Shamsel-Din, Mohsen M. T. El-Tahawy, Ayman A. Ibrahim","doi":"10.1515/ract-2023-0175","DOIUrl":null,"url":null,"abstract":"Recently, tumor-targeted radionuclide therapy has gained much recognition for the treatment of metastasized cancer. There is a growing interest in using the theranostic radionuclide <jats:sup>47</jats:sup>Sc, owing to its excellent chemical and nuclear properties. However, the available chelating agents require a relatively high temperature for their radiolabeling, which could denature biomolecules. The aim of the present study is to synthesize a dipeptide agent that forms a thermodynamically more stable complex with <jats:sup>47</jats:sup>Sc at room temperature. A novel <jats:italic>α</jats:italic>-amino acid ester derivative attached to pyrazine and tetrazole heterocyclic rings has been prepared by the azide coupling method. Different spectroscopic methods (FT-IR, <jats:sup>1</jats:sup>H NMR, and mass spectra) were used for characterization of the target compound. The newly synthesized dipeptide was radiolabeled with <jats:sup>47</jats:sup>Sc, and a high radiochemical yield of 98.5 ± 1.5 % and <jats:italic>in vitro</jats:italic> serum stability up to 72 h were attained at room temperature within 20 min. The quantum chemical calculations at B3PW91/6-31G(d) level were employed to establish the molecular structure of the dipeptide and its complexation with <jats:sup>47</jats:sup>Sc. The selectivity of <jats:sup>47</jats:sup>Sc-dipeptide toward localization in tumor cells was performed by molecular docking on different receptors in addition to <jats:italic>in vivo</jats:italic> biodistribution on solid tumor-bearing mice. A high T/NT ratio of 8.16 was obtained after 4 h p.i, suggesting that this complex could be used as a potential cancer theranostic agent.","PeriodicalId":21167,"journal":{"name":"Radiochimica Acta","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiochimica Acta","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1515/ract-2023-0175","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
Abstract
Recently, tumor-targeted radionuclide therapy has gained much recognition for the treatment of metastasized cancer. There is a growing interest in using the theranostic radionuclide 47Sc, owing to its excellent chemical and nuclear properties. However, the available chelating agents require a relatively high temperature for their radiolabeling, which could denature biomolecules. The aim of the present study is to synthesize a dipeptide agent that forms a thermodynamically more stable complex with 47Sc at room temperature. A novel α-amino acid ester derivative attached to pyrazine and tetrazole heterocyclic rings has been prepared by the azide coupling method. Different spectroscopic methods (FT-IR, 1H NMR, and mass spectra) were used for characterization of the target compound. The newly synthesized dipeptide was radiolabeled with 47Sc, and a high radiochemical yield of 98.5 ± 1.5 % and in vitro serum stability up to 72 h were attained at room temperature within 20 min. The quantum chemical calculations at B3PW91/6-31G(d) level were employed to establish the molecular structure of the dipeptide and its complexation with 47Sc. The selectivity of 47Sc-dipeptide toward localization in tumor cells was performed by molecular docking on different receptors in addition to in vivo biodistribution on solid tumor-bearing mice. A high T/NT ratio of 8.16 was obtained after 4 h p.i, suggesting that this complex could be used as a potential cancer theranostic agent.