title: SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT.
abstract: Iodine-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) is a useful SPECT tracer for imaging the dopamine transporter. Its slow kinetics, however, necessitate imaging on the day after the injection. Two N-omega-fluoroalkyl analogs of beta-CIT, the fluoropropyl and fluoroethyl compounds (beta-CIT-FP and beta-CIT-FE, respectively), characterized by faster kinetics in baboons, were tested in humans as potential tracers for the dopamine transporter. Four healthy volunteers were injected with [123I]-beta-CIT-FP and another four were injected with [123I]beta-CIT-FE. SPECT data were acquired for 1149 +/- 590 min and 240 +/- 30 min, respectively. Both tracers demonstrated high brain uptake (6.37% +/- 0.37% and 7.8% +/- 1.5% of the injected dose, respectively). Activity concentrated with time in the striatal area, reaching a peak within 30 min, with little or no washout for [123I]beta-CIT-FP and a faster washout for [123I]beta-CIT-FE (14.7% +/- 6.9%). Occipital and midbrain activity showed similar patterns, displaying a peak within 15 min and rapid washout, followed by stable levels at approximately 100 min for both tracers. The ratio of peak specific striatal-to-peak specific midbrain activity was 9.1 +/- 1.8 for [123I]beta-CIT-FP and 7.7 +/- 0.7 for [123I]beta-CIT-FE, showing high in vivo selectivity for the dopamine transporter. These preliminary results suggest that both compounds could be used as SPECT (labeled with 123I) or PET (labeled with 18F) radiotracers to image the dopamine transporters in the living human brain.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, USA.
authors.forename: A
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: M S
authors.initials: MS
authors.lastname: Gandelman
authors.forename: G A
authors.initials: GA
authors.lastname: DeErausquin
authors.forename: Y
authors.initials: Y
authors.lastname: Zea-Ponce
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: M
authors.initials: M
authors.lastname: Laruelle
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003287:Contrast Media; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009662:Nortropanes / Q000493:pharmacokinetics; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics
chemical_list: D002352:Carrier Proteins; D003287:Contrast Media; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C097058:N-(2-fluoroethyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine