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Journal of Lipid Research, Vol. 50, 1259-1268, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

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

John C. Umhau^1,*, 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.^**

^* Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892
^** Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892
Yale University School of Medicine, New Haven, CT 06520-8042
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892
PET Department, National Institutes of Health Clinical Center, Bethesda, MD, 20892
^*** Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298
Molecular Tracer, Bethesda, MD 20814

This research was supported by the Intramural Research Programs of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, and National Institute on Aging.

Published, JLR Papers in Press, December 26, 2008.

¹ To whom correspondence should be addressed. e-mail: umhau{at}jhu.edu

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 [1-¹¹C]DHA mostly entered nonbrain organs, with 0.5% entering the 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 regional 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 2.5 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.

Supplementary key words metabolism • blood flow • n-3 polyunsaturated fatty acid

Abbreviations: ARA, arachidonic acid; DHA, docosahexaenoic acid; MR, magnetic resonance; PET, positron emission tomography; PLA₂, phospholipase A₂; PVE, partial volume error; rCBF, regional cerebral blood flow; ROI, regions of interest

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