Current development of sigma-2 receptor radioligands as potential tumor imaging agents

Sigma receptors are transmembrane proteins with two different subtypes: σ₁ and σ₂. Because of its overexpression in tumors, the σ₂ receptor (σ₂R) is a well-known biomarker for cancer cells. A large number of small-molecule ligands for the σ₂Rs have been identified and tested for imaging the proliferative status of tumors using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These small molecules include derivatives of bicyclic amines, indoles, cyclohexylpiperazines and tetrahydroisoquinolines. This review discusses various aspects of small molecule ligands, such as chemical composition, labeling strategy, affinity for σ₂Rs, and in vitro/in vivo investigations. The recent studies described here could be useful for the development of σ₂R radioligands as potential tumor imaging agents.