Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]SA4503

Nisha Kuzhuppilly Ramakrishnan; Anniek Visser; Anna Rybczynska; Csaba Nyakas; Paulus Luiten; Chantal Kwizera; Jurgen Sijbesma; Philippus Elsinga; Kiichi Ishiwata; Rudi Dierckx; Aren van Waarde

doi:10.1007/s11307-015-0917-6

Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]SA4503

Nisha Kuzhuppilly Ramakrishnan
, Anniek Visser
, Anna Rybczynska
, Csaba Nyakas
, Paulus Luiten
, Chantal Kwizera
, Jurgen Sijbesma
, Philippus Elsinga
, Kiichi Ishiwata
, Rudi Dierckx
, Aren van Waarde^*

^*Corresponding author for this work

Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Research output: Contribution to journal › Article › Academic › peer-review

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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 [C-11]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.

Original language	English
Pages (from-to)	588-597
Number of pages	10
Journal	Molecular Imaging and Biology
Volume	18
Issue number	4
DOIs	https://doi.org/10.1007/s11307-015-0917-6
Publication status	Published - Aug-2016

Keywords

Senescence
Sigma-1 receptor
Agonist binding
Positron emission tomography
Kinetic modeling
Brainstem
Hypothalamus
EXTRACELLULAR ACETYLCHOLINE LEVEL
SPONTANEOUS GLUTAMATE RELEASE
POSITRON-EMISSION-TOMOGRAPHY
CENTRAL-NERVOUS-SYSTEM
AGE-RELATED-CHANGES
RECEPTOR LIGANDS
PRELIMBIC CORTEX
FRONTAL-CORTEX
IN-VIVO
SITES

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Sigma-1 Agonist Binding in the Aging Rat BrainFinal publisher's version, 1.2 MBLicence: GNU GPL

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title = "Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]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 [C-11]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.",

keywords = "Senescence, Sigma-1 receptor, Agonist binding, Positron emission tomography, Kinetic modeling, Brainstem, Hypothalamus, EXTRACELLULAR ACETYLCHOLINE LEVEL, SPONTANEOUS GLUTAMATE RELEASE, POSITRON-EMISSION-TOMOGRAPHY, CENTRAL-NERVOUS-SYSTEM, AGE-RELATED-CHANGES, RECEPTOR LIGANDS, PRELIMBIC CORTEX, FRONTAL-CORTEX, IN-VIVO, SITES",

author = "\{Kuzhuppilly Ramakrishnan\}, Nisha and Anniek Visser and Anna Rybczynska and Csaba Nyakas and Paulus Luiten and Chantal Kwizera and Jurgen Sijbesma and Philippus Elsinga and Kiichi Ishiwata and Rudi Dierckx and \{van Waarde\}, Aren",

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doi = "10.1007/s11307-015-0917-6",

language = "English",

volume = "18",

pages = "588--597",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

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T1 - Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]SA4503

AU - Kuzhuppilly Ramakrishnan, Nisha

AU - Visser, Anniek

AU - Rybczynska, Anna

AU - Nyakas, Csaba

AU - Luiten, Paulus

AU - Kwizera, Chantal

AU - Sijbesma, Jurgen

AU - Elsinga, Philippus

AU - Ishiwata, Kiichi

AU - Dierckx, Rudi

AU - van Waarde, Aren

PY - 2016/8

Y1 - 2016/8

N2 - 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 [C-11]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.

AB - 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 [C-11]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.

KW - Senescence

KW - Sigma-1 receptor

KW - Agonist binding

KW - Positron emission tomography

KW - Kinetic modeling

KW - Brainstem

KW - Hypothalamus

KW - EXTRACELLULAR ACETYLCHOLINE LEVEL

KW - SPONTANEOUS GLUTAMATE RELEASE

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - CENTRAL-NERVOUS-SYSTEM

KW - AGE-RELATED-CHANGES

KW - RECEPTOR LIGANDS

KW - PRELIMBIC CORTEX

KW - FRONTAL-CORTEX

KW - IN-VIVO

KW - SITES

U2 - 10.1007/s11307-015-0917-6

DO - 10.1007/s11307-015-0917-6

M3 - Article

SN - 1536-1632

VL - 18

SP - 588

EP - 597

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 4

ER -

Sigma-1 agonist binding in the aging rat brain: A microPET study with [11C]SA4503

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Keywords

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