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

Ramakrishnan, Nisha; Visser, Anniek; Rybczynska, Anna; Nyakas, Csaba; Luiten, Paul; Kwizera, Chantal; Sijbesma, Jurgen; Elsinga, Philip; Ishiwata, Kiichi; Dierckx, Rudi; van Waarde, Aren; Ramakrishnan, Nisha K; Visser, Anniek K D; Rybczynska, Anna A; Nyakas, Csaba J; Luiten, Paul G M; Sijbesma, Jurgen W A; Elsinga, Philip H; Dierckx, Rudi A J O

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.

SENILE dementia; LABORATORY rats; POSITRON emission tomography; RADIOACTIVITY; ALZHEIMER'S disease; BRAIN metabolism; AGING; ANIMAL experimentation; BIOLOGICAL models; BRAIN; CELL receptors; DYNAMICS; HETEROCYCLIC compounds; METABOLISM; RADIOISOTOPES; RATS; THREE-dimensional imaging

Molecular Imaging & Biology, 2016, Vol 18, Issue 4, p588

1536-1632

Academic Journal

10.1007/s11307-015-0917-6