Molecular Probes for Imaging the Sigma-2 Receptor: In Vitro and In Vivo Imaging Studies

The sigma-2 (σ₂) receptor has been validated as a biomarker of the proliferative status of solid tumors. Therefore, radiotracers having a high affinity and high selectivity for σ₂ receptors have the potential to assess the proliferative status of human tumors using noninvasive imaging techniques such as Positron Emission Tomography (PET). Since the σ₂ receptor has not been cloned, the current knowledge of this receptor has relied on receptor binding studies with the radiolabeled probes and investigation of the effects of the σ₂ receptor ligands on tumor cells. The development of the σ₂ selective fluorescent probes has proven to be useful for studying subcellular localization and biological functions of the σ₂ receptor, for revealing pharmacological properties of the σ₂ receptor ligands, and for imaging cell proliferation. Preliminary clinical imaging studies with [¹⁸F]ISO-1, a σ₂ receptor probe, have shown promising results in cancer patients. However, the full utility of imaging the σ₂ receptor status of solid tumors in the diagnosis and prediction of cancer therapeutic response will rely on elucidation of the functional role of this protein in normal and tumor cell biology.