title: Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography.
abstract: Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-(11)C]DHA mostly entered nonbrain organs, with approximately 0.5% entering the brain. Then, using PET and intravenous [1-(11)C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [(15)O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate J(in), the product of K*, and the unesterified plasma DHA concentration equaled 3.8 +/- 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-(11)C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease.
authors.affiliation: Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. umhau@jhu.edu
authors.forename: John C
authors.initials: JC
authors.lastname: Umhau
authors.forename: Weiyin
authors.initials: W
authors.lastname: Zhou
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Alla
authors.initials: A
authors.lastname: Polozova
authors.forename: James
authors.initials: J
authors.lastname: Demar
authors.forename: Nahed
authors.initials: N
authors.lastname: Hussein
authors.forename: Abesh K
authors.initials: AK
authors.lastname: Bhattacharjee
authors.forename: Kaizong
authors.initials: K
authors.lastname: Ma
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.forename: Sharon
authors.initials: S
authors.lastname: Majchrzak
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kurdziel
authors.forename: Norman
authors.initials: N
authors.lastname: Salem
mesh_terms: D000328:Adult; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D000882:Haplorhini; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism; D012039:Regional Blood Flow; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D004281:Docosahexaenoic Acids