Positron Emission Tomography Imaging of Human Brain Phospholipid Metabolism in Relation to Age and Disease
The Brain Physiology and Metabolism Section (BPMS) of the National Institute on Aging (NIA)
and the Clinical Neuroscience Program (CNP) of the National Institute of Neurological
Disorders and Stroke (NINDS) propose to study regional brain phospholipid metabolism in
young and old normal volunteers and in patients with Alzheimer disease. The method to be
employed, developed from animal studies, involves the intravenous injection of a
radiolabeled polyunsaturated fatty acid, [11C]arachidonic acid and measuring regional brain
radioactivity using positron emission tomography (PET). A mathematical model is used to
calculate regional brain incorporation coefficients k* of [11C]arachidonate into brain.
These reflect brain signal transduction and membrane turnover involving phospholipids and
the signal transduction and membrane turnover involving phospholipids and the activation of
the enzyme, phospholipase A2. PET also will be used in the same subjects to measure
regional cerebral blood flow (rCBF), a marker of brain energy metabolism, with radioactive
water (H20). The literature reports that rCBF and energy metabolism decline with age
and are markedly reduced in Alzheimer disease. We hypothesize that (a) we will be able to
quantify and image incorporation of [11C]arachidonate into the human brain for the first
time, (b) in normal volunteers, k* for arachidonate will be correlated on a regional basis
with rCBF, (c) rCBF will be reduced in the older compared with the younger normal
volunteers, and markedly reduced in Alzheimer disease patients compared with the older
volunteers (controls), (d) the normal coupling (regression) relation between k* and rCBF
will be disturbed in Alzheimer disease.
This protocol originally proposed to measure brain incorporation of two labeled fatty acids,
[11C]arachidonate and [11C]palmitate, as well as rCBF, in young and old normal volunteers,
and in patients with Alzheimer disease, Niemann-Pick Type C disease and brain tumors.
Eleven patients with Alzheimer disease have been scanned using [11C]arachidonate and
H20, compared with 10 volunteers. The current amendment proposes to use only
[11C]arachidonate and H20 in 16 additional normal volunteers, and to compare the
results between old and young groups and patients with Alzheimer disease. A request to
study only 16 additional normal volunteers was approved by the NINDS IRB at the Continuing
Review in 1999, and has not changed since then.
United States: Federal Government
|National Institute of Neurological Disorders and Stroke (NINDS)||Bethesda, Maryland 20892|