Journal of Lipid Research (Jul 2009)
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,
- Norman Salem, Jr.
Affiliations
- John C. Umhau
- 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
- Weiyin Zhou
- 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
- Richard E. Carson
- 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
- Stanley I. Rapoport
- 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
- Alla Polozova
- 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
- James Demar
- 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
- Nahed Hussein
- 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
- Abesh K. Bhattacharjee
- 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
- Kaizong Ma
- 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
- Giuseppe Esposito
- 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
- Sharon Majchrzak
- 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
- Peter Herscovitch
- 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
- William C. Eckelman
- 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
- Karen A. Kurdziel
- 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
- 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
- Journal volume & issue
-
Vol. 50,
no. 7
pp. 1259 – 1268
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 [1-11C]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 Jin, 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.
