The utility of 11C-arachidonate PET to study in vivo dopaminergic neurotransmission in humans

Abstract

We developed a novel method to study dopaminergic neurotransmission using positron emission tomography (PET) with 1-11Carachidonic acid (1-11CAA). Previous preclinical studies have shown the utility of 1-11CAA as a marker of signal transduction coupled to cytosolic phospholipase A2 (cPLA2). Using 1-11CAA and 15 Owater PET, we measured regional incorporation coefficients K for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D 1/D2 agonist (10 or 20μg/kg subcutaneous) apomorphine. We confirmed a robust central dopaminergic response to apomorphine by observing significant increases in the serum concentration of growth hormone. We observed significant increases, as well as decreases in K* and increases in rCBF in response to apomorphine. These changes remained significant after covarying for handedness and apomorphine dosage. The magnitude of increases in K* was lower than those in our previous animal experiments, likely reflecting the smaller dose of apomorphine used in the current human study. Changes in K* may reflect neuronal signaling downstream of activated D2-like receptors coupled to cPLA2. Changes in rCBF are consistent with previous studies showing net functional effects of D1/D2 activation. 1- 11CAA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia. © 2012 ISCBFM All rights reserved.