title: Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment.
abstract: Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [99mTc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3x5 mg/day). All subjects were injected with 800 MBq [99mTc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semiquantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [99mTc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43+/-0.18 vs 1.22+/-0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00+/-0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs.
authors.affiliation: Department of Nuclear Medicine, University of Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dresel
authors.forename: J
authors.initials: J
authors.lastname: Krause
authors.forename: K H
authors.initials: KH
authors.lastname: Krause
authors.forename: C
authors.initials: C
authors.lastname: LaFougere
authors.forename: K
authors.initials: K
authors.lastname: Brinkbäumer
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: K
authors.initials: K
authors.lastname: Hahn
authors.forename: K
authors.initials: K
authors.lastname: Tatsch
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000627:therapeutic use*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C493214:SLC6A3 protein, human; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1; D008774:Methylphenidate; D004298:Dopamine