title: Assessment of fetal brain uptake of paraquat in utero using in vivo PET/CT imaging.
abstract: 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.affiliation: Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Bartlett
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.forename: R Jerome
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: James E
authors.initials: JE
authors.lastname: Holden
authors.forename: Onofre T
authors.initials: OT
authors.lastname: DeJesus
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging; D001921:Brain / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008253:Macaca mulatta; D064847:Multimodal Imaging / Q000379:methods*; D010269:Paraquat / Q000493:pharmacokinetics* / Q000633:toxicity; D049268:Positron-Emission Tomography; D011247:Pregnancy; D014057:Tomography, X-Ray Computed
chemical_list: D010269:Paraquat