Brain incorporation of [11C]arachidonic acid in young healthy humans measured with positron emission tomography.
Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A2. The goal of this study was to establish an in vivo quantitative method to examine the role of AA in this signaling process in the human brain. A simple irreversible uptake model was derived from rat studies and modified for positron emission tomography (PET) to quantify the incorporation rate K* of [11C]AA into brain. Dynamic 60-minute three-dimensional scans and arterial input functions were acquired in 8 young healthy adults studied at rest. Brain radioactivity was corrected for uptake of the metabolite [11C]CO2. K* and cerebral blood volume (Vb) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6+/-1.2 and 2.6+/-0.5 microL x min(-1) x mL(-1) in gray and white matter, respectively. K* and Vb values were found to be unchanged with data analysis periods from 20 to 60 minutes. Thus, PET can be used to obtain quantitative images of the incorporation rate K* of [11C]AA in the human brain. As brain incorporation of labeled AA has been shown in awake rats to be increased by pharmacological activation associated with phospholipase A2-signaling, PET and [11C]AA may be useful to measure signal transduction in the human brain.
Giovacchini
Giampiero
G
Brain Physiology and Metabolism Section, National Institute on Aging, Bethesda, Maryland, U.S.A.
Chang
Michael C J
MC
Channing
Michael A
MA
Toczek
Maria
M
Mason
Alicja
A
Bokde
Arun L W
AL
Connolly
Catherine
C
Vuong
Bik-Kee
BK
Ma
Ying
Y
Der
Margaret G
MG
Doudet
Doris J
DJ
Herscovitch
Peter
P
Eckelman
William C
WC
Rapoport
Stanley I
SI
Carson
Richard E
RE
D000328:Adult; D016718:Arachidonic Acid / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D014055:Tomography, Emission-Computed / Q000379:methods*
D002250:Carbon Radioisotopes; D010743:Phospholipids; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2