Document Detail


Biodistribution and blood metabolism of 1-11C-methyl-4-piperidinyl n-butyrate in humans: an imaging agent for in vivo assessment of butyrylcholinesterase activity with PET.
MedLine Citation:
PMID:  15585478     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1-(11)C-Methyl-4-piperidinyl n-butyrate ((11)C-MP4B) is a new radiopharmaceutical for the in vivo assessment of butyrylcholinesterase (BuChE) activity using PET. To quantify in vivo activity of BuChE with a kinetic model, investigators must determine the time course of radioactivity associated with unchanged (11)C-MP4B. We aimed at clarifying the metabolic fate and whole-body distribution of intravenously administered (11)C-MP4B in man. METHODS: High-performance liquid chromatography and thin-layer chromatography assays were performed to determine the amounts of intact (11)C-MP4B and its radioactive hydrolysis product in blood withdrawn during PET. In addition, we evaluated the distribution and kinetics of (11)C-MP4B uptake in human brain and main organs. RESULTS: The analysis of plasma samples of 28 human subjects (10 patients with Alzheimer's disease [AD] and 18 healthy controls) showed that the level of unmetabolized (11)C-MP4B decreases rapidly from 28% +/- 14% (mean +/- SD) at 0.5 min to 7% +/- 6% at 15 min after injection. Large individual variation was observed in the rate of plasma (11)C-MP4B hydrolysis, but no significant differences were found in the degradation of (11)C-MP4B either between male and female or between healthy subjects and patients. The whole-body distribution of (11)C-MP4B showed the highest activities in the urinary bladder, renal pelvis, stomach, salivary glands, liver, kidneys, spleen, vertebral column, and brain. In patients with AD, (11)C-MP4B activity in the brain was highest in cerebellum, followed by striatum, pons, and thalamus. Lower (11)C-MP4B activity was seen in cortical areas. CONCLUSION: Our results indicate that (11)C-MP4B is excreted rapidly through the renal system. Careful analysis of plasma metabolites is required to determine the accurate arterial input function for quantitative PET measurement. Biodistribution of (11)C-MP4B in the brains of patients with AD appears to be in accordance with the distribution of BuChE seen in postmortem studies of human brain, except for the observed higher activity in striatum than in cortex. Further studies of the cerebral distribution and regional kinetic analysis of (11)C-MP4B are in progress.
Authors:
Anne Roivainen; Juha Rinne; Jere Virta; Tarja Järvenpää; Satu Salomäki; Miexiang Yu; Kjell Någren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  45     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-08     Completed Date:  2005-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2032-9     Citation Subset:  IM    
Affiliation:
Turku PET Centre, Turku University Hospital, FI-20521 Turku, Finland. anne.roivainen@pet.tyks.fi
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alzheimer Disease / enzymology*,  radionuclide imaging
Brain / radionuclide imaging*
Butyrates / diagnostic use*
Butyrylcholinesterase / metabolism*
Carbon Radioisotopes / diagnostic use*,  pharmacokinetics
Chromatography, High Pressure Liquid
Female
Humans
Male
Middle Aged
Piperidines / diagnostic use*
Positron-Emission Tomography / methods*
Chemical
Reg. No./Substance:
0/Butyrates; 0/Carbon Radioisotopes; 0/Piperidines; 0/methyl-4-piperidinyl n-butyrate; EC 3.1.1.-/Butyrylcholinesterase

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