title: Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [(11)C]SA4503.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Some areas showed reductions of ligand binding with aging whereas binding in other areas (cortex) was not significantly affected.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.|Division of Imaging Sciences and Biomedical Engineering, King's College London, Strand, London, WC2R 2LS, UK.
authors.forename: Nisha K
authors.initials: NK
authors.lastname: Ramakrishnan
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Anniek K D
authors.initials: AK
authors.lastname: Visser
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Rybczynska
authors.affiliation: Research Group of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.|Department of Morphology and Physiology, Semmelweis University, 17 Vas, H-1088, Budapest, Hungary.
authors.forename: Csaba J
authors.initials: CJ
authors.lastname: Nyakas
authors.affiliation: Research Group of Molecular Neurobiology, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.|Department of Morphology and Physiology, Semmelweis University, 17 Vas, H-1088, Budapest, Hungary.
authors.forename: Paul G M
authors.initials: PG
authors.lastname: Luiten
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kwizera
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Jurgen W A
authors.initials: JW
authors.lastname: Sijbesma
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.affiliation: Southern Tohoku Research Institute for Neuroscience, 7-115 Yatsuyamada, Koriyama, 963-8052, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. a.van.waarde@umcg.nl.
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002250:Carbon Radioisotopes; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D008297:Male; D055442:Metabolome; D008954:Models, Biological; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism; D014018:Tissue Distribution; D000097605:Sigma-1 Receptor
chemical_list: D002250:Carbon Radioisotopes; D010879:Piperazines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C101789:SA 4503
keywords: Agonist binding; Brainstem; Hypothalamus; Kinetic modeling; Positron emission tomography; Senescence; Sigma-1 receptor