title: Dopamine D(2) receptor quantification in extrastriatal brain regions using [(123)I]epidepride with bolus/infusion.
abstract: The iodinated benzamide epidepride, which shows a picomolar affinity binding to dopamine D(2) receptors, has been designed for in vivo studies using SPECT. The aim of the present study was to apply a steady-state condition by the bolus/infusion approach with [(123)I]epidepride for the quantification of striatal and extrastriatal dopamine D(2) receptors in humans. In this way the distribution volume of the tracer can be determined from a single SPECT image and one blood sample. Based on bolus experiments, an algorithm using conventional convolution arguments for prediction of the outcome of a bolus/infusion (B/I) experiment was applied. It was predicted that a B/I protocol with infusion of one-third of the initial bolus per hour would be appropriate. Steady-state conditions were attained in extrastriatal regions within 3-4 h but the infusion continued up to 7 h in order to minimize the significance of individual differences in plasma clearance and binding parameters. A steady-state condition, however, could not be attained in striatal brain regions using a B/I protocol of 20 h, even after 11 h. Under near steady-state conditions a striatal:cerebellar ratio of 23 was demonstrated. Epidepride has a unique signal-to-noise ratio compared to [(123)I]IBZM but present difficulties for steady-state measurements of striatal regions. The bolus/infusion approach is particularly feasible for quantification of the binding potential in extrastriatal regions.
authors.affiliation: Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark. pinborg@pet.rh.dk
authors.forename: L H
authors.initials: LH
authors.lastname: Pinborg
authors.forename: C
authors.initials: C
authors.lastname: Videbaek
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: C G
authors.initials: CG
authors.lastname: Swahn
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: L
authors.initials: L
authors.lastname: Friberg
authors.forename: O B
authors.initials: OB
authors.lastname: Paulson
authors.forename: N A
authors.initials: NA
authors.lastname: Lassen
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D006706:Homeostasis; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001549:Benzamides; D003287:Contrast Media; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C063525:epidepride