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Multiinjection approach for D2 receptor binding quantification in living rats using [11C]raclopride and the β-microprobe: crossvalidation with in vitro binding data.
- Source :
- Journal of Cerebral Blood Flow & Metabolism; Nov2005, Vol. 25 Issue 11, p1517-1527, 11p, 1 Diagram, 1 Chart, 4 Graphs
- Publication Year :
- 2005
-
Abstract
- The purpose of this study was to quantify D<subscript>2</subscript> receptors density and affinity in living rats using [<superscript>11</superscript>C]raclopride and to validate the multiinjection modelling approach. To this aim, we used an intracerebral β<superscript>+</superscript>-sensitive probe as a highly sensitive system to quantify the radioligand activity using a single three-injection experimental paradigm. The study was divided into three main parts: (i) [<superscript>11</superscript>C]raclopride catabolism evaluation without and with cimetidine pretreatment (cytochrome P<subscript>450</subscript> inhibitor); (ii) quantification of kinetics parameters in the striatum, enthorinal cortex, and cerebellum of living rats using a three-compartment model with an arterial input function; (iii) correlation study of in vivo and in vitro binding density and affinity values in the same striatal tissues. (i) raclopride catabolism was very reproducible between individuals; cimetidine pre-treatment resulted in a 30% reduction of raclopride metabolites. (ii) D<subscript>2</subscript> striatal B′<subscript>max</subscript> and K<subscript>d</subscript>V<subscript>r</subscript> estimates obtained by compartmental modelling were 19.87±6.45 and 6.2±3.3 nmol/L, respectively. Cerebellum is the best candidate as a reference region with no specific binding detectable in vivo. (iii) When comparing density (B<subscript>max</subscript>/B′<subscript>max</subscript>) and affinity (K<subscript>d</subscript>/K<subscript>d</subscript>V<subscript>r</subscript>) values in vivo and in vitro for each striatum, a high strict correlation was found (r<superscript>2</superscript>=0.90 and 0.72, for density and affinity, respectively). These results validate the multi-injection modelling approach coupled to β-microprobe acquisitions as a mean to provide accurate and separate estimates of dopamine D<subscript>2</subscript>-receptor density and affinity, in the living rodent striatum.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1517–1527. doi:10.1038/sj.jcbfm.9600141; published online 25 May 2005 [ABSTRACT FROM AUTHOR]
- Subjects :
- BLOOD circulation
BLOOD flow
HEMODYNAMICS
BIOCHEMISTRY
MICROPROBE analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0271678X
- Volume :
- 25
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Journal of Cerebral Blood Flow & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22404532
- Full Text :
- https://doi.org/10.1038/sj.jcbfm.9600141