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

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

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6 Citations (Scopus)


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 [11C]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 (VT) and binding potential (BPND) of the tracer. BPND 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.

Original languageEnglish
Pages (from-to)588-597
Number of pages10
JournalMolecular Imaging and Biology
Issue number4
Publication statusPublished - Aug 1 2016


  • Agonist binding
  • Brainstem
  • Hypothalamus
  • Kinetic modeling
  • Positron emission tomography
  • Senescence
  • Sigma-1 receptor

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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    Ramakrishnan, N. K., Visser, A. K. D., Rybczynska, A. A., Nyakas, C. J., Luiten, P. G. M., Kwizera, C., Sijbesma, J. W. A., Elsinga, P. H., Ishiwata, K., Dierckx, R. A. J. O., & van Waarde, A. (2016). Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [11C]SA4503. Molecular Imaging and Biology, 18(4), 588-597.