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

Paweł K Halik, Piotr F J Lipiński, Joanna Matalińska, Przemysław Koźmiński, Aleksandra Misicka, Ewa Gniazdowska

Molecules (Basel, Switzerland) 2020 Aug 18

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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.

Citation

Paweł K Halik, Piotr F J Lipiński, Joanna Matalińska, Przemysław Koźmiński, Aleksandra Misicka, Ewa Gniazdowska. Radiochemical Synthesis and Evaluation of Novel Radioconjugates of Neurokinin 1 Receptor Antagonist Aprepitant Dedicated for NK1R-Positive Tumors. Molecules (Basel, Switzerland). 2020 Aug 18;25(16)