Document Detail


Maternal and fetal 11C-cocaine uptake and kinetics measured in vivo by combined PET and MRI in pregnant nonhuman primates.
MedLine Citation:
PMID:  15695792     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cocaine use during pregnancy has been shown to be deleterious to the infant. This may reflect reduction of flow to placenta or effects on the fetal brain. Methods to assess pharmacokinetics of drugs of abuse in vivo would be useful to investigate the mechanisms underlying the fetal adverse effects. We recently reported that combined MRI and PET technology allows the measurement of radioisotope distribution in maternal and fetal organs in pregnant Macaca radiata. Here, we evaluate the utility of PET to measure the uptake and distribution of (11)C-cocaine in the third-trimester fetus. METHODS: Six pregnant M. radiata weighing 3.8-9.0 kg were anesthetized and MR images were acquired on a 4-T MRI instrument. In all 6 animals, dynamic PET scans were subsequently acquired using 148-259 MBq of (11)C-cocaine. Time-activity curves for both maternal and fetal organs were obtained simultaneously with the pregnant animal positioned transverse in the PET scanner. Distribution volume ratios for maternal and fetal brain for (11)C-cocaine were calculated. RESULTS: Coregistration of PET and MR images allowed identification of fetal organs and brain regions and demonstrated that (11)C-cocaine or its labeled metabolites readily cross the placenta and accumulate mainly in fetal liver and to a lesser extent in the brain. Time to reach peak (11)C uptake in brain was shorter for the mother than for the fetus. The distribution volume ratios of the maternal striatum were higher than those of the fetus. Placenta was clearly visible on the early time frames and showed more rapid uptake and clearance than other fetal tissues. CONCLUSION: The pregnant M. radiata model allows the noninvasive measurement of radioisotope pharmacokinetics in maternal and fetal brain and other organs simultaneously. Although the uptake of radioactivity into the fetal brain after the injection of (11)C-cocaine is lower and slower than in the maternal brain, a measurable quantity of (11)C-cocaine (or its labeled metabolites) accumulates in the fetal brain at early times after injection. The highest accumulation of (11)C occurs in the fetal liver. Rapid radioisotope accumulation and clearance in the placenta offer potential as an input function for kinetic modeling for future studies of binding site availability.
Authors:
Helene Benveniste; Joanna S Fowler; William Rooney; Yu-Shin Ding; Angela L Baumann; Daryn H Moller; Congwu Du; Walter Backus; Jean Logan; Pauline Carter; Jeremy D Coplan; Anat Biegon; Leonard Rosenblum; Bruce Scharf; John S Gatley; Nora D Volkow
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  46     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-07     Completed Date:  2005-04-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  312-20     Citation Subset:  IM    
Affiliation:
Medical Department, Brookhaven National Laboratory, Upton, New York 11793, USA. Benveniste@bnl.gov
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MeSH Terms
Descriptor/Qualifier:
Aging / metabolism
Animals
Brain / embryology*,  metabolism,  radionuclide imaging*
Carbon Isotopes / diagnostic use,  pharmacokinetics
Cocaine / diagnostic use,  pharmacokinetics*
Female
Fetus / metabolism,  radionuclide imaging
Image Interpretation, Computer-Assisted / methods*
Kinetics
Macaca radiata
Magnetic Resonance Imaging / methods*
Maternal-Fetal Exchange / physiology
Metabolic Clearance Rate
Organ Specificity
Positron-Emission Tomography / methods*
Pregnancy
Pregnancy, Animal*
Radiopharmaceuticals / diagnostic use,  pharmacokinetics
Subtraction Technique
Tissue Distribution
Grant Support
ID/Acronym/Agency:
1R21DA0015545/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 0/Radiopharmaceuticals; 50-36-2/Cocaine

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


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