Presymptomatic diagnosis of experimental Parkinsonism with 123I-PE2I SPECT.
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.
Prunier
Caroline
C
INSERM U316, Laboratoire de Biophysique médicale et Pharmaceutique, 31 avenue Monge, 37200 Tours, France. c.prunier@chu-tours.fr
Bézard
Erwan
E
Montharu
Jérôme
J
Mantzarides
Marina
M
Besnard
Jean-Claude
JC
Baulieu
Jean-Louis
JL
Gross
Christian
C
Guilloteau
Denis
D
Chalon
Sylvie
S
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
D015259:Dopamine Agents; C402415:I123-PE2I; D007457:Iodine Radioisotopes; D009662:Nortropanes; D019275:Radiopharmaceuticals; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine