title: 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-(11)C]arachidonic acid ([1-(11)C]AA). Previous preclinical studies have shown the utility of [1-(11)C]AA as a marker of signal transduction coupled to cytosolic phospholipase A(2) (cPLA(2)). Using [1-(11)C]AA and [(15)O]water PET, we measured regional incorporation coefficients K(*) for AA and regional cerebral blood flow (rCBF), respectively, in healthy male volunteers given the D(1)/D(2) 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 D(2)-like receptors coupled to cPLA(2). Changes in rCBF are consistent with previous studies showing net functional effects of D(1)/D(2) activation. [1-(11)C]AA PET may be useful for studying disturbances of dopaminergic neurotransmission in conditions such as Parkinson's disease and schizophrenia.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. thambisettym@mail.nih.gov
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Gallardo
authors.forename: Jeih-San
authors.initials: JS
authors.lastname: Liow
authors.forename: Lori L
authors.initials: LL
authors.lastname: Beason-Held
authors.forename: John C
authors.initials: JC
authors.lastname: Umhau
authors.forename: Abesh K
authors.initials: AK
authors.lastname: Bhattacharjee
authors.forename: Margaret
authors.initials: M
authors.lastname: Der
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000328:Adult; D001058:Apomorphine / Q000008:administration & dosage; D016718:Arachidonic Acid / Q000008:administration & dosage*; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism*; D002247:Carbon Isotopes / Q000008:administration & dosage; D002560:Cerebrovascular Circulation / Q000502:physiology*; D018491:Dopamine Agonists / Q000008:administration & dosage; D059290:Dopaminergic Neurons / Q000000981:diagnostic imaging / Q000378:metabolism*; D007839:Functional Laterality / Q000502:physiology; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011188:Potassium / Q000378:metabolism; D011859:Radiography; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D002247:Carbon Isotopes; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016718:Arachidonic Acid; D054513:Group IV Phospholipases A2; D001058:Apomorphine; D011188:Potassium