Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors

Cancer ranks among the top triumvirate leading causes of human deaths worldwide. The pathological mechanisms are notably intricate, demonstrating proliferative and metastatic capabilities, which complicate therapeutic interventions. The sigma-1 receptor (sigma 1R) plays a crucial role in tumor survival and migration, while the sigma-2 receptor (sigma 2R) is intimately associated with tumor proliferation. This review encapsulated the investigation concerning sigma 1R and sigma 2R in neoplasms and rigorously summarized the ligands and radio-ligands development and their tumor applications, such as antitumor cell proliferation and PET/SPECT imaging in tumors. A comprehensive classification discussion was undertaken regarding the chemical structures and emphasized the possibility of dual/multitargeted ligands. Ultimately, we discussed the effects of chiral structures and the pharmacological characteristics of ligands on affinity and pharmacokinetic features in vivo, particularly concerning radiopharmaceuticals. This review functions as a beneficial resource, fostering ligand deployment and stimulating the generation of innovative ideas for developing innovative radiopharmaceuticals.