title: Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]beta-CIT.
abstract: The effect of subchronic treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporters (DAT) was examined in patients with idiopathic Parkinson's disease with SPECT (single photon emission computed tomography) using [123I]beta-CIT (2beta-carbomethoxy-3beta-[4-iodophenyl]tropane) as the radiotracer. Patients who were not currently being treated with these medications were given either 750 mg L-dopa/carbidopa per day (n = 8) or 10 mg L-selegiline per day (n = 8). [123I]beta-CIT imaging was performed three times in each patient: at baseline before treatment, while on medication and after 4-6 weeks of drug treatment, and following withdrawal from medication (approximately 1 week for L-dopa/carbidopa and 9 weeks for L-selegiline). Comparison of scans 2 and 3 provided a measure of drug occupancy of the [123I]beta-CIT binding site; comparison of scans 1 and 2 provided a measure of both up- or downregulation of DAT levels and drug occupancy following subchronic drug treatment. DAT levels were assessed from an image acquired approximately 22 hours after radiotracer injection as a ratio of regional brain activities: (striatum - occipital)/occipital. Striatal DAT levels were not significantly different when any two of the three scans were compared for both drug treatments. These results suggest that typical clinical doses of L-dopa/carbidopa and L-selegiline do not induce significant occupancy of the [123I]beta-CIT binding site and that 4-6 weeks of treatment causes no significant modulation of DAT levels. These results support the validity of measuring DAT levels with [123I]beta-CIT without the need to withdraw patients from medication treatment.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, VA Connecticut at West Haven 06516, USA.
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
authors.forename: K L
authors.initials: KL
authors.lastname: Marek
authors.forename: K
authors.initials: K
authors.lastname: Sheff
authors.forename: S
authors.initials: S
authors.lastname: Zoghbi
authors.forename: J
authors.initials: J
authors.lastname: Castronuovo
authors.forename: A
authors.initials: A
authors.lastname: Feigin
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001692:Biological Transport; D002230:Carbidopa / Q000627:therapeutic use*; D003042:Cocaine / Q000031:analogs & derivatives*; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D012642:Selegiline / Q000494:pharmacology / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D007457:Iodine Radioisotopes; D012642:Selegiline; D007980:Levodopa; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D008995:Monoamine Oxidase; D003042:Cocaine; D002230:Carbidopa; D004298:Dopamine