title: SPECT imaging of dopamine transporter sites in normal and MPTP-Treated rhesus monkeys.
abstract: Parkinson's disease is characterized by degeneration of dopamine (DA) neurons and their terminals. Since these neurons contain dopamine transporters (DAT), radioligands that bind to these sites are promising radiopharmaceuticals for diagnosis and therapeutic monitoring of disease progression. We evaluated [123I]-2 beta-carbomethoxy- 3 beta-(4-fluorophenyl)-N-(1-iodoprop-1-en-3-yl)nortropane ([123I]IACFT) for SPECT imaging in an MPTP model of parkinsonism.
  
  
  METHODS
  Three rhesus monkeys were imaged before and at 1 and 2 mo after treatment with MPTP. The SPECT results were correlated with motor behavior and PET imaging with [11C]-2 beta-carbomethoxy-3 beta-aryltropane ([11C]-CFT). Also, biodistribution was measured by planar imaging.
  
  
  RESULTS
  In normal animals, striatal accumulation of radioactivity was rapid and peaked within 30 min. Striatal accumulation of [123I]IACFT was nearly completely displaceable with unlabeled CFT (1 mg/kg) but was not affected by a similar dose of the serotonin (5-HT) transport inhibitor, citalopram. The striatal to cerebellar ratio measured at 30 min, after injection of [123I]IACFT was significantly higher (p < 0.01) than with [11C]CFT; approximately 6; 1 versus approximately 2.5; 1. After MPTP treatment this ratio decreased to 1.02:1 with IACFT and 1.23:1 with [11C]CFT. Blood clearance of [123I]IACFT was rapid with a terminal t1/2 of approximately 30 min. HPLC of plasma samples demonstrated that the concentration of intact ligand decreases rapidly, approaching zero by 60 min. Low levels of accumulation were measured in extracranial tissues.
  
  
  CONCLUSIONS
  These results demonstrate that [123I]IACFT is an excellent SPECT ligand for dopamine transporter sites that combines the critical characteristics of: (a) high striatal to cerebellar ratios, (b) high selectivity for dopamine versus 5-HT transporter sites, (c) convenient preparation at high-specific activity and radiochemical purity and (d) a striatal localization rate that is well matched to the physical t1/2 of 123I.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: J W
authors.initials: JW
authors.lastname: Babich
authors.forename: D R
authors.initials: DR
authors.lastname: Elmaleh
authors.forename: S A
authors.initials: SA
authors.lastname: Barrow
authors.forename: P
authors.initials: P
authors.lastname: Meltzer
authors.forename: R N
authors.initials: RN
authors.lastname: Hanson
authors.forename: B K
authors.initials: BK
authors.lastname: Madras
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D003042:Cocaine / Q000031:analogs & derivatives*; D003287:Contrast Media; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009662:Nortropanes / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000000981:diagnostic imaging*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002352:Carrier Proteins; D003287:Contrast Media; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C102282:N-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine