Neuroimaging of sigma-1 receptors with positron emission tomography.

In view of the involvement of sigma-1 receptors in different pathways related to the pathogenesis of various neuropsychiatric diseases and considering the neuroprotective potential of drugs targeting sigma-1 receptors quantitative neuroimaging by positron emission tomography (PET) is regarded as an unique method to investigate sigma-1 receptors in the progress of disease and under therapy. Alterations of sigma-1 receptor densities have been found in psychiatric disorders, neurodegeneration and cancer. Molecular receptor imaging with PET may provide a significant contribution to the understanding of the cross-talk between these receptors and inter- and intracellular signalling systems in these diseases. However the applicability of this imaging approach is still hampered due to lack of suitable radiopharmaceuticals for routine use. Although [¹¹C]SA4503 has been used in human studies for already 10 years its broad clinical applicability is limited. Recent efforts made to develop ¹⁸F-labelled PET radiotracers for targeting the sigma-1 receptors in the human brain are presented. The current status of the evaluation of the most favourable radiolabelled compounds, including [¹⁸F]fluspidine, in animal models and humans will be discussed. New insights into the function of sigma-1 receptors in human brain will allow a better diagnosis of brain and cancerous diseases and direct a rational development of new therapeutic concepts.