Radiochemical Synthesis and Evaluation of Novel Radioconjugates of Neurokinin 1 Receptor Antagonist Aprepitant Dedicated for NK1R-Positive Tumors

Abstract

Aprepitant, a lipophilic and small molecular representative of neurokinin 1 receptor antagonists, is known for its anti-proliferative activity on numerous cancer cell lines that are sensitive to Substance P mitogen action. In the presented research, we developed two novel structural modifications of aprepitant to create aprepitant conjugates with different radionuclide chelators. All of them were radiolabeled with ⁶⁸Ga and ¹⁷⁷Lu radionuclides and evaluated in terms of their lipophilicity and stability in human serum. Furthermore, fully stable conjugates were examined in molecular modelling with a human neurokinin 1 receptor structure and in a competitive radioligand binding assay using rat brain homogenates in comparison to the aprepitant molecule. This initial research is in the conceptual stage to give potential theranostic-like radiopharmaceutical pairs for the imaging and therapy of neurokinin 1 receptor-overexpressing cancers.