Computational studies of target-specific radiopharmaceuticals for theranostics

Radiopharmaceuticals are key tools in nuclear medicine, enabling both diagnostic imaging and targeted therapy for conditions such as cancer and neurological disorders. The integration of computational techniques in the drug-discovery process, such as molecular docking and molecular dynamics simulations, contributes to the development of this class of compounds. Here we review recent computational studies on radiopharmaceuticals acting on different targets: receptors, enzymes, and transporters. Several receptors such as chemokine receptor 4, neurokinin-1, metabotropic glutamate receptor, and gastrin-releasing peptide receptor have been investigated using molecular simulations to optimize ligand binding and enhance receptor targeting. Enzymes like prostate-specific membrane antigen and fibroblast activation protein α have been investigated in silico for their interaction with novel radiopharmaceutical inhibitors. Additionally, transporter proteins such as glucose transporters have been explored for their role in cancer metabolism and imaging applications. Advanced computational studies, including quantum mechanics calculations and free energy estimations, have contributed to our understanding of radiopharmaceutical binding modes and stability at the molecular level of detail. The review highlights the potential of computational approaches for cost-effective design of next-generation theranostic agents, emphasizing the importance of molecular databases in ligand-based drug discovery and artificial intelligence-based drug design.