Document Detail


Assessment of fetal brain uptake of paraquat in utero using in vivo PET/CT imaging.
MedLine Citation:
PMID:  21546347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prenatal in utero conditions are thought to play a role in the development of adult diseases including Parkinson's disease (PD). Paraquat is a common herbicide with chemical structure similar to 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine, a neurotoxin known to induce parkinsonism. In order to assess the role of in utero paraquat exposure in PD, uptake in maternal and fetal brains were measured using positron emission tomography (PET)/computed tomography (CT) imaging. Two anesthetized pregnant rhesus macaques in the late second trimester of pregnancy were given bolus iv injections of ¹¹C-paraquat, and whole-body PET/CT imaging was performed. Using maternal ventricular blood pool as the input function, the unidirectional influx rate constants (K(i)s), a measure of the irreversible transport of paraquat from plasma to brain, were calculated for the maternal and fetal brains using Patlak graphical analysis. Results indicate minimal uptake of paraquat by both maternal and fetal brains with average K(i)s of 0.0009 and 0.0016 per minute, respectively. The highest regional cerebral uptake in the maternal brain (0.0009% injected dose) was seen in the pineal gland, a structure known to lack a blood brain barrier. The finding of minimal paraquat uptake in maternal and fetal brains is similar to previous findings in adult male macaques and extends the contention that a single acute paraquat exposure, prenatally or postnatally, is unlikely to play a role in PD.
Authors:
Rachel M Bartlett; Dhanabalan Murali; R Jerome Nickles; Todd E Barnhart; James E Holden; Onofre T DeJesus
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-04
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  122     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-15     Completed Date:  2011-12-19     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  551-6     Citation Subset:  IM    
Affiliation:
Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier / radionuclide imaging
Brain / metabolism*
Female
Fetus / drug effects*
Macaca mulatta
Paraquat / pharmacokinetics*,  toxicity
Positron-Emission Tomography and Computed Tomography / methods*
Pregnancy
Grant Support
ID/Acronym/Agency:
CA09206/CA/NCI NIH HHS; P51 RR000167/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
4685-14-7/Paraquat
Comments/Corrections

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


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