Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography

John C. Umhau, Weiyin Zhou, Richard E. Carson, Stanley I. Rapoport, Alla Polozova, James Demar, Nahed Hussein, Abesh K. Bhattacharjee, Kaizong Ma, Giuseppe Esposito, Sharon Majchrzak, Peter Herscovitch, William C. Eckelman, Karen A. Kurdziel, and Norman Salem . Jr

Lab of Clinical and Translational Studies, National Intitute on Alcohol Abuse and Alcoholism, Bethesda, Md 20854

Corresponding Author: umhau{at}nih.gov

Docosahexaenoic acid (DHA, 22:6n-3) is a critical constituent of 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 [1-¹¹C]DHA mostly entered non-brain organs, with approximately 0.5% entering brain. Then, using PET and intravenous [1-¹¹C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged cerebral blood flow (rCBF) using PET and intravenous [¹⁵O]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 two and a half years. Thus, PET with [1-¹¹C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and disease.

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