title: In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography.
abstract: This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled haloperidol (0.7 mg total dosage), and once in an unblocked state. Blood sampling and SPECT were performed intermittently during 6 hours after intravenous [123I]IBZM bolus injection. Plasma [123I]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and plasma protein binding was determined by equilibrium dialysis. In humans, the striatal D2/D3 receptor occupancy was 0.27+/-0.085 and the in vivo Kd for haloperidol was 0.25+/-0.1 nmol/L, which is comparable to Kd values as obtained from in vitro studies. The authors conclude that steady-state [123I]IBZM SPECT studies allow for determination of dopamine D2/D3 receptor occupancy in striatum and in vivo measurement of drug affinity to striatal dopamine D2 and D3 receptors.
authors.affiliation: Neurobiology Research Unit, University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Videbaek
authors.forename: K
authors.initials: K
authors.lastname: Toska
authors.forename: L
authors.initials: L
authors.lastname: Friberg
authors.forename: S
authors.initials: S
authors.lastname: Holm
authors.forename: H R
authors.initials: HR
authors.lastname: Angelo
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001549:Benzamides / Q000493:pharmacokinetics*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001549:Benzamides; C493593:DRD3 protein, human; C493595:Drd3 protein, rat; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D006220:Haloperidol