Document Detail


Development of a simultaneous PET/microdialysis method to identify the optimal dose of 11C-raclopride for small animal imaging.
MedLine Citation:
PMID:  15848236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the field of small animal positron emission tomography (PET), the assumptions underlying human and primate kinetic models may not be sustained in rodents. That is, the threshold dose at which a pharmacologic response occurs may be lower in small animals. In order to define this relationship, we combined microPET imaging using 11C-raclopride with microdialysis measures of extracellular fluid (ECF) dopamine (DA). In addition, we performed a series of studies in which a known mass of raclopride was microinfused into one striatum prior to a high specific activity (SA) systemic injection of 11C-raclopride. This single-injection approach provided a high and low SA region of radiotracer binding in the same animal during the same scanning session. Our data demonstrate that the binding potential (BP) declines above 3.5 pmol/ml (0.35 microg), with an ED50 of 8.55+/-5.62 pmol/ml. These data also provide evidence that BP may be compromised by masses of raclopride below 2.0 pmol/ml (0.326 microg). Increases in ECF DA were produced by mass doses of raclopride over 3.9 pmol/ml (0.329 microg) with an ED50 of 8.53+/-2.48 pmol/ml. Taken together, it appears that an optimal range of raclopride mass exists between 2.0 and 3.5 pmol/ml, around which the measured BP can be compromised by system sensitivity, endogenous DA, or excessive competition with unlabeled compound.
Authors:
Wynne K Schiffer; David L Alexoff; Colleen Shea; Jean Logan; Stephen L Dewey
Related Documents :
23897816 - Glia maturation factor (gmf) interacts with arp2/3 complex in a nucleotide state-depend...
8868286 - In vivo evaluation of [11c]- and [18f]-labelled cocaine analogues as potential dopamine...
2568936 - [3h]sch 23390 labels dopamine d-1 receptor sites in the rat kidney.
7595496 - Hydrophobic residues of the d2 dopamine receptor are important for binding and signal t...
6694516 - Characterization of norepinephrine binding to plasma proteins of the dog and the rabbit.
9636026 - Colocalization of heparin and receptor binding sites on keratinocyte growth factor.
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-08
Journal Detail:
Title:  Journal of neuroscience methods     Volume:  144     ISSN:  0165-0270     ISO Abbreviation:  J. Neurosci. Methods     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-25     Completed Date:  2005-07-15     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  7905558     Medline TA:  J Neurosci Methods     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  25-34     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Binding, Competitive / drug effects
Brain / anatomy & histology,  metabolism,  radionuclide imaging*
Brain Mapping
Carbon Isotopes / blood,  pharmacokinetics*
Dopamine Antagonists / blood,  pharmacokinetics*
Dose-Response Relationship, Drug
Functional Laterality
Male
Microdialysis / methods*
Positron-Emission Tomography / methods*
Raclopride / blood,  pharmacokinetics*
Rats
Rats, Sprague-Dawley
Time Factors
Grant Support
ID/Acronym/Agency:
F31 DA015874/DA/NIDA NIH HHS; F31-DA15874/DA/NIDA NIH HHS; K02 DA022346/DA/NIDA NIH HHS; R01 DA015041/DA/NIDA NIH HHS; R01 DA015041/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/Dopamine Antagonists; 430K3SOZ7G/Raclopride
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Unsupervised clustering algorithm for N-dimensional data.
Next Document:  Histological, behavioural and neurochemical evaluation of medial forebrain bundle and striatal 6-OHD...