The Utility of 11 C-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 [1-¹¹C]arachidonic acid ([1-¹¹C]AA). Previous preclinical studies have shown the utility of [1-¹¹C]AA as a marker of signal transduction coupled to cytosolic phospholipase A₂ (cPLA₂). Using [1-¹¹C]AA and [¹⁵O]water PET, we measured regional incorporation coefficients K* for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D₁/D₂ agonist (10 or 20 μg/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. [1-¹¹C]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia.