[I-123]-CIT SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease

Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
Neurology (Impact Factor: 8.29). 02/1996; 46(1):231-7. DOI: 10.1212/WNL.46.1.231
Source: PubMed


We have used in vivo single-photon emission computed tomography (SPECT) of the dopamine transporter with 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) to investigate striatal dopamine transporter loss in patients with early Parkinson's disease (PD). Striatal uptake of ([123I] beta-CIT was compared in eight early-PD patients with exclusively hemi-parkinsonism and eight age- and sex-matched healthy subjects. [123I] beta-CIT striatal uptake was reduced by approximately 53% contralateral and by 38% ipsilateral to the clinically symptomatic side in the hemi-PD patients, compared with the mean striatal uptake in age- and sex-matched healthy subjects. The relative reduction in [123I] beta-CIT uptake in the hemi-PD patients was greater in the putamen than in the caudate. These data demonstrate that SPECT imaging of the dopamine transporter with [123I] beta-CIT can identify patients with PD at the onset of motor symptoms and suggest that this technique also may be useful in identifying individuals with developing dopaminergic pathology before onset of motor symptoms.

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    • "A decrease in DAT binding at striatal presynaptic terminals is associated with the loss of functional neuronal activity that characterizes PD. Significant DAT changes may precede the onset of clinical symptoms [22]. Decreased striatal [ 123 I]b-CIT binding has been reported in anosmic relatives of patients with PD who do not themselves have clinical evidence of parkinsonism [23]. "

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    • "Further research is required in order to identify whether the deteriorated cognitive performances can be imputed to the large DAT binding increase in the caudate, ventral striatum and anterior putamen or to the more restricted DAT binding decrease in the posterior putamen that we report here on a restricted number of cases. The asymmetrical manifestation of motor symptoms in PD patients is well recognized and used as a hallmark of Parkinson's disease (Marek et al., 1996), and a recent SPECT study in humans PD patients showed a lateralization of DAT availability in the posterior putamen Fig. 6. Comparison between recovered and symptomatic state. "
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    ABSTRACT: The delayed appearance of motor symptoms in PD poses a crucial challenge for early detection of the disease. We measured the binding potential of the selective dopamine active transporter (DAT) radiotracer [(11)C]PE2I in MPTP-treated macaque monkeys, thus establishing a detailed profile of the nigrostriatal DA status following MPTP intoxication and its relation to induced motor and non-motor symptoms. Clinical score and cognitive performance were followed throughout the study. We measured longitudinally in vivo the non-displaceable binding potential to DAT in premotor, motor-recovered (i.e. both non-symptomatic) and symptomatic MPTP-treated monkeys. Results show an unexpected and pronounced dissociation between clinical scores and [(11)C]PE2I-BPND during the premotor phase i.e. DAT binding in the striatum of premotor animals was increased around 20%. Importantly, this broad increase of DAT binding in the caudate, ventral striatum and anterior putamen was accompanied by i) deteriorated cognitive performance, showing a likely causal role of the observed hyperdopaminergic state (Cools, 2011; Cools and D'Esposito, 2011) and ii) an asymmetric decrease of DAT binding at a focal point of the posterior putamen, suggesting that increased DAT is one of the earliest, intrinsic compensatory mechanism. Following spontaneous recovery from motor deficits, DAT binding was greatly reduced as recently shown in-vivo with other radiotracers (Blesa et al., 2010, 2012). Finally, high clinical scores were correlated to considerably low levels of DAT only after the induction of a stable parkinsonian state. We additionally show that the only striatal region which was significantly correlated to the degree of motor impairments is the ventral striatum. Further research on this period should allow better understanding of DA compensation at premature stages of PD and potentially identify new diagnosis and therapeutic index.
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    • "These transporters normally function to reuptake dopamine from the synaptic cleft. The DAT plays a crucial role in the maintenance of the presynaptic neuron and is reduced 50-70% in patients with Parkinson's [19] [20] [21]. Several studies show a high correlation between abnormal DaTscan and a final diagnosis of either PD or MSA via autopsy although the DaTscan cannot distinguish between the different PS disorders [22] [23]. "
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