Brain Incorporation of [¹¹C]Arachidonic Acid in Young Healthy Humans Measured with Positron Emission Tomography

Abstract

Summary: Arachidonic acid (AA) is an important second messenger involved in signal transduction mediated by phospholipase A 2 . 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 [ 11 C]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 [ 11 C]CO 2 . K* and cerebral blood volume (V b ) were estimated pixel-by-pixel and were calculated in regions of interest. K* equaled 5.6 ± 1.2 and 2.6 ± 0.5 L · min −1 · mL −1 in gray and white matter, respectively. K* and V b 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 [ 11 C]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 A 2 -signaling, PET and [ 11 C]AA may be useful to measure signal transduction in the human brain.

DHA brain uptake and APOE4 status: a PET study with [1-11C]-DHA

“…The lower value of k * in the medial temporal cortex is consistent with previous reports for [1- 11 C]- arachidonic acid and with values for rCBF [29, 30]. The data likely reflect the unique architecture of this region, although there is some effect of the PVE correction [24].…”

11C-Labeled Analogs of Indomethacin Esters and Amides for Brain Cyclooxygenase-2 Imaging: Radiosynthesis, in Vitro Evaluation and in Vivo Characteristics in Mice

“…However, it remains controversial the extent to which non-specific binding to plasma proteins inhibits BBB penetration. This theory cannot explain why some radiotrac- 34,35) with calculated log PϾ7 have been used successfully in PET experiments although their maximal brain uptakes are lower than those of commonly used neuroreceptor radioligands. Therefore, lipophilicity is, in any case, an imperfect proxy for BBB permeability.…”

[Carboxyl‐11C]Labelling of Four High‐Affinity cPLA2α Inhibitors and Their Evaluation as Radioligands in Mice by Positron Emission Tomography

“…Thus, “first‐generation” radioligands for cPLA2α are likely to contain a carboxyl group. Because of extensive ionization at physiological pH, [ 11 C]carboxylic acids (p K a ≈4) do not generally cross the blood–brain barrier (BBB), but some, such as [ 11 C]arachidonic acid (clog D , 4.89) do enter brain, even if only to a limited extent . In this study, the carboxyl group also provided a generic site for labelling with carbon‐11 ( t 1/2 =20.4 min).…”

“…[8,14] So far,o nly [ 11 C]arachidonic acid has been used with PET for preclinical and clinical imaging [15,16] to explore brain cPLA2 activity. [17] However,b ecause of the involvement of arachidonic acid in neural functions other than signal transduction, such as membrane synthesis and remodelling, the incorporation rate (K*) has not been deemede ntirely specific to the cPLA2 signalling system. [17] Many selectivei nhibitors of cPLA2a are known.…”