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

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 47 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 47 Sc 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, 1 H NMR, and mass spectra) were used for characterization of the target compound. The newly synthesized dipeptide was radiolabeled with 47 Sc, 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 47 Sc. The selectivity of 47 Sc-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.