Document Detail


Kinetic analysis of the cannabinoid-1 receptor PET tracer [(18)F]MK-9470 in human brain.
MedLine Citation:
PMID:  20033684     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [(18)F]MK-9470 in human brain. METHODS: [(18)F]MK-9470 data were analysed using reversible models and the distribution volume V (T) and V (ND) k (3) (V (ND) k (3) = K (1) k (2)) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K (i) and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined. RESULTS: A reversible two-tissue compartment model using a global k (4) value was necessary to describe brain kinetics. Both V (T) and V (ND) k (3) were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K (i). The linear relationship between K (i) and V (ND) k (3) demonstrated that K (i) or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K (i) and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics. CONCLUSION: [(18)F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [(18)F]MK-9470 plasma kinetics can be assessed using a few venous samples.
Authors:
Sandra Marina Sanabria-Bohórquez; Terence G Hamill; Karolien Goffin; Inge De Lepeleire; Guy Bormans; H Donald Burns; Koen Van Laere
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2009-12-24
Journal Detail:
Title:  European journal of nuclear medicine and molecular imaging     Volume:  37     ISSN:  1619-7089     ISO Abbreviation:  Eur. J. Nucl. Med. Mol. Imaging     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101140988     Medline TA:  Eur J Nucl Med Mol Imaging     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  920-33     Citation Subset:  IM    
Affiliation:
Imaging, Merck Research Laboratories, Sumneytown Pike WP44D-2, West Point, PA 19486, USA. sandra_sanabria@merck.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Brain / metabolism*
Cerebrovascular Circulation
Feasibility Studies
Female
Humans
Kinetics
Male
Middle Aged
Models, Biological
Positron-Emission Tomography*
Pyridines / blood,  diagnostic use,  metabolism*,  pharmacokinetics*
Radioactive Tracers
Receptor, Cannabinoid, CB1 / metabolism*
Young Adult
Chemical
Reg. No./Substance:
0/MK-9470; 0/Pyridines; 0/Radioactive Tracers; 0/Receptor, Cannabinoid, CB1
Comments/Corrections
Comment In:
Eur J Nucl Med Mol Imaging. 2010 May;37(5):917-9   [PMID:  20358196 ]

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


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