title: Presymptomatic diagnosis of experimental Parkinsonism with 123I-PE2I SPECT.
abstract: Presymptomatic diagnosis of the loss of nigrostriatal neurons that characterises Parkinson's disease, is a crucial issue for future neuroprotective therapies as degeneration exceeds 70 to 80% when symptoms appear. Here we propose an early diagnosis method that utilises single photon emission computerized tomography (SPECT) coupled to the iodine-123-labelled selective dopamine transporter ligand N-(3-ioprop-2E-enyl)-2-beta-(4-methylphenyl)nortropane ((123)I-PE2I), applying Logan's graphical method for quantification. Sequential (123)I-PE2I SPECT acquisitions were performed in nonhuman primates chronically treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine according to a regimen that consistently produces a progressive Parkinsonian state. While classical neurological examination only allows detection of Parkinsonian signs at Day 12 of the protocol of intoxication, the mean distribution volume ratio calculated according to Logan's graphical method is significantly decreased from Day 6 onward, i.e., when animals are clinically normal. (123)I-PE2I SPECT is a very sensitive method to detect presymptomatic lesions of nigrostriatal neurons and the first to be experimentally validated. It could now be used clinically for early diagnosis and follow-up of neuroprotective treatment.
authors.affiliation: INSERM U316, Laboratoire de Biophysique médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France. c.prunier@chu-tours.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Prunier
authors.forename: Erwan
authors.initials: E
authors.lastname: Bézard
authors.forename: Jérôme
authors.initials: J
authors.lastname: Montharu
authors.forename: Marina
authors.initials: M
authors.lastname: Mantzarides
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Besnard
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Baulieu
authors.forename: Christian
authors.initials: C
authors.lastname: Gross
authors.forename: Denis
authors.initials: D
authors.lastname: Guilloteau
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015259:Dopamine Agents; D005260:Female; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D009662:Nortropanes / Q000493:pharmacokinetics; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015259:Dopamine Agents; C402415:I123-PE2I; D007457:Iodine Radioisotopes; D009662:Nortropanes; D019275:Radiopharmaceuticals; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine