title: A double-injection technique for in vivo measurement of dopamine D2-receptor density in monkeys with 3-(2'-[18F]fluoroethyl)spiperone and dynamic positron emission tomography.
abstract: Dopamine D2-receptor density in striatum of monkey was measured with 3-(2'-[18F]fluoroethyl)spiperone (FESP) and dynamic positron emission tomography (PET), using a double-injection technique. A first bolus of high specific activity (SA) FESP (5 mCi; approximately equal to 1 Ci/mumol) was injected i.v.; 90 min later, a second bolus of lower SA FESP (5 mCi; approximately equal to 0.04 Ci/mumol) was injected. A dynamic PET study was performed to measure the kinetics of FESP in striatum over 180 min, and the metabolite-corrected concentration of FESP in plasma as a function of time was obtained from arterial blood samples. A nonlinear compartmental model that took into account the saturability of the receptor binding was used to describe the kinetics of FESP in striatum. Model parameters were estimated by regression with a constraint based on information about the equilibrium dissociation constant of the ligand-receptor binding. Dopamine D2-receptor density in striatum was estimated to be 25.9 +/- 12.7 pmol/g in seven Macaca nemestrina monkeys. The method does not require the use of cerebellum as a reference tissue region and an estimate of dopamine D2-receptor density can be obtained from a single study.
authors.affiliation: Department of Radiological Sciences, UCLA School of Medicine 90024-1721.
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: M M
authors.initials: MM
authors.lastname: Bahn
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: N
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: R A
authors.initials: RA
authors.lastname: Hawkins
authors.forename: J C
authors.initials: JC
authors.lastname: Mazziotta
authors.forename: M E
authors.initials: ME
authors.lastname: Phelps
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D007275:Injections, Intravenous; D007700:Kinetics; D008254:Macaca nemestrina; D008433:Mathematics; D008959:Models, Neurological; D008962:Models, Theoretical; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C051175:3-N-(2-fluoroethyl)spiperone; D013134:Spiperone