Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [(11)C]SA4503

PURPOSE: Sigma-1 receptor ligands modulate the release of several neurotransmitters and intracellular calcium signaling. We examined the binding of a radiolabeled sigma-1 agonist in the aging rat brain with positron emission tomography (PET). PROCEDURES: Time-dependent uptake of [(11)C]SA4503 was measured in the brain of young (1.5 to 3 months) and aged (18 to 32 months) Wistar Hannover rats, and tracer-kinetic models were fitted to this data, using metabolite-corrected plasma radioactivity as input function. RESULTS: In aged animals, the injected probe was less rapidly metabolized and cleared. Logan graphical analysis and a 2-tissue compartment model (2-TCM) fit indicated changes of total distribution volume (V(T)) and binding potential (BP(ND)) of the tracer. BP(ND) was reduced particularly in the (hypo)thalamus, pons, and medulla. CONCLUSIONS: Some areas showed reductions of ligand binding with aging whereas binding in other areas (cortex) was not significantly affected. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11307-015-0917-6) contains supplementary material, which is available to authorized users.