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Lega Italiana Per La Lotta Contro La Malattia Di Parkinson Le Sindromi Extrapiramidali E Le Demenze

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Lega Italiana Per La Lotta Contro La Malattia Di Parkinson Le Sindromi Extrapiramidali E Le Demenze LIMPE lega italiana per la lotta contro la malattia di parkinson le sindromi extrapiramidali e le demenze Web site: http://www.parkinson-limpe.it/ XXIX National Congress Lecce 23–25 October 2002 Parkinson Parkinsonism Dementia: from Biotechnology to Medical Management SELECTED SHORT PAPERS Scientific Committee Bruno Bergamasco, Giovanni U. Corsini, Mario Manfredi, Stefano Ruggieri, Pierfranco Spano Secretariat LIMPE Viale dell’Università 30, 00185 Roma Tel. and Fax: +39-06-4455618 E-mail: [email protected] Neurol Sci (2003) 24:149–150 DOI 10.1007/s10072-003-0103-5 123I-Ioflupane/SPECT binding to to the dopamine transporter (DAT) may be better suited and provide more-accurate estimation of degeneration. Several striatal dopamine transporter (DAT) tracers that bind to DAT and utilize SPECT are available; uptake in patients with Parkinson’s they are all cocaine derivatives. The most widely used are disease, multiple system atrophy, and [123I]β-CIT and 123I-Ioflupane ([123I]FP-CIT) [3, 4]. The main advantage of 123I-Ioflupane is that a steady state allow- progressive supranuclear palsy ing SPECT imaging is reached 3 h after a single bolus injec- 1 2 1 tion of the radioligand, compared with the 18–24 h required A. Antonini (౧) • R. Benti • R. De Notaris 1 1 1 for [123I]β-CIT. Therefore DAT imaging with 123I-Ioflupane S. Tesei • A. Zecchinelli • G. Sacilotto 1 1 1 1 can be completed the same day. N. Meucci • M. Canesi • C. Mariani • G. Pezzoli 123 P. Gerundini2 Several studies have demonstrated the usefulness of I- 1 Centro per la malattia di Parkinson, Dipartimento di Ioflupane SPECT imaging in the diagnosis of parkinsonism. Neuroscienze, Istituti Clinici di Perfezionamento, Via Bignami 1, A sensitivity of 97% has been reported for the identification Milan, Italy of nigrostriatal degeneration in Parkinson’s disease (PD) [5]. 2 Medicina Nucleare IRCCS-Ospedale Maggiore, Milan, Italy Limited data are available on DAT binding in other degener- ative parkinsonisms, such as progressive supranuclear palsy Abstract We used SPECT and the tracer 123I-Ioflupane to (PSP) or multiple system atrophy (MSA) [6]. measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson’s dis- ease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were Patients and methods compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three We studied DAT binding with 123I-Ioflupane SPECT in 70 PD forms of parkinsonism. However, decrements were signifi- patients (age 62±13 years, disease duration 5±4 years), 10 MSA-P cantly greater in PSP (0.51±0.39, p<0.01) compared with patients (age 60±8 years, disease duration 4±2 years), and 10 PSP MSA-P (0.70±0.33) and PD (0.95±0.38). No differences patients (age 64±8 years, disease duration 4±3 years). UPDRS were found between MSA and PD. Putamen/caudate ratios scores were obtained in all patients in “off” condition. Brain SPECT was performed with a dedicated triple detector were greater in PSP (0.83±0.12, p<0.01) than in PD gamma camera (Prism 3000, Philips) equipped with ultra-high-res- (0.51±0.11), suggesting a more-uniform involvement of olution fan beam collimators. 123I-Iofluopane (DATScan) (110–140 dopamine nerve terminals in both caudate nucleus and puta- MBq) was administered intravenously 30–40 min after thyroid men. Our results confirm that DAT binding can provide an blockade. SPECT studies were acquired 3–4 h later and reconstruc- accurate and highly sensitive measure of dopamine degener- tion was performed by applying an iterative algorithm, followed by ation. PSP patients may show a different pattern of neuronal tridimensional filtering. Transaxial sections were attenuation cor- loss compared with MSA and PD. rected and reoriented with respect to the canthomeatal plane. Four adjacent sections, including striatum and occipital cortex, were summed in a single 2.56-cm thick slice for quantitative analysis. Irregular regions of interest (ROIs) were drawn on both striata, put- amina, heads of caudate nuclei, and mesial occipital cortices. Degenerative parkinsonian syndromes are characterized by Iofluopane specific binding ratio was expressed as (striatal ROI progressive loss of dopaminergic neurons in the substantia counts – occipital ROI counts)/(occipital ROI counts) and calculat- nigra. Neuroimaging studies allow in vivo assessment of the ed for the whole striatum, putamen, and caudate head of each hemi- nigro-striatal dopaminergic system and the extent of neu- sphere. We also calculated putamen/caudate ratios for each subject. ronal loss in these disorders. Tracers that bind selectively to dopamine cells have been applied together with positron emission tomography (PET), and more recently single-pho- ton emission computed tomography (SPECT), for clinical and research purposes. Historically, 18F-fluorodopa/PET was Results considered the gold standard for assessment of dopaminergic denervation [1, 2]. There are, however, technical limitations We found significant decrements in DAT binding in the stria- to the use of this tracer. Firstly, PET is available at few cen- tum of PD, MSA-P, and PSP patients compared with healthy ters. Secondly, it is likely that dopa-decarboxylase activity is controls. Mean striatal values were 0.95±0.38 in PD, upregulated early in the disease process, resulting in an 0.70±0.33 in MSA, and 0.51±0.39 in PSP. Healthy controls underestimation of dopaminergic neuronal loss. Therefore have striatal uptake values >1.7. An example of 123I-Ioflupane tracers that utilize the SPECT technique and bind selectively SPECT in a control subject, a PD patient, and a PSP patient is 150 The differential diagnosis of different forms of parkin- sonism is not easy, particularly at an early stage. Although a recent report suggests that in a specialized tertiary center diagnostic accuracy can be as high as 90%, clinical patho- logical studies in the 1990s found the accuracy of clinical diagnosis to be only 76% [7], and the rate of misdiagnosis at Healthy control early stages of the disease may exceed this figure. In a recent community based study conducted in a general practice, the diagnosis of clinically probable PD could only be confirmed in 53% of patients taking antiparkinsonian drugs [8]. Such misdiagnosis can lead to inappropriate management strate- gies that may include further unnecessary investigations. Parkinson’s disease In conclusion, studies of the pre-synaptic dopaminergic system may prove clinically useful in assessing the presence and extent of nigro-striatal loss in different forms of degen- erative parkinsonism. Additional neuroimaging investiga- tions, such as 123I-IBZM for striatal dopamine receptors or 1,ST magnetic resonance imaging, may help to characterize Progressive supranuclear palsy these patients. The finding of a uniform and profound DAT loss in the whole striatum seems to be specific to PSP. Fig. 1 123I-Ioflupane SPECT in a control subject, a PD patient, and a PSP patient References shown in Fig. 1. We found that striatal values were signifi- cantly lower in PSP than PD (p<0.01). No differences were 1. Antonini A, Vontobel P, Psylla M, Günther I, Maguire R, found between MSA-P and PD. Putamen/caudate ratios were Missimer J, Leenders KL (1995) Complementary PET studies greater in PSP (0.83±0.12, p<0.01) than in PD (0.51±0.11) of the striatal dopaminergic system in Parkinson’s Disease. and MSA-P (0.60±0.12). In PD patients we found a signifi- Arch Neurol 52:1183–1192 cant correlation with UPDRS motor scores (p<0.001). No 2. Brooks DJ, Ibanez V, Sawle GV et al (1990) Differing patterns correlation was found in the MSA and PSP cohorts. of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 28:547–555 3. Asenbaum S, Pirker W, Angelberger P, Bencsits G, Pruckmayer M, Brucke T (1998) [123I]beta-CIT and SPECT Discussion in essential tremor and Parkinson’s disease. Journal Neural Transm 105:1213–1228 We found significant decrements of striatal DAT in PD, 4. Booij J, Andringa G, Rijks LJ et al (1997) 123I-FP-CIT binds MSA-P, and PSP patients. We can confirm that 123I-Ioflupane to the dopamine transporter as assessed by biodistribution SPECT binding is a sensitive measurement of the dopamin- studies in rats and SPECT studies in MPTP-lesioned mon- ergic system in degenerative parkinsonsim. Moreover, we keys. Synapse 27:183–190 5. Benamer TS, Patterson J, Grosset DG et al (2000) Accurate found a different pattern of degeneration between PD and differentiation of parkinsonism and essential tremor using PSP. A similar finding has been previously reported with the visual assessment of [123I]-FP-CIT SPECT imaging: the 18 tracer F-fluorodopa in PSP patients [2]. The greater decre- [123I]-FP-CIT study group. Mov Disord 15:503–510 ments in the putamen than in the caudate nucleus in PD 6. Lucignani G, Gobbo C, Moresco RM, Antonini A et al (2002) patients is consistent with neuropathological data showing The feasibility of statistical parametric mapping for the analy- that the bulk of nigral loss affects the dopaminergic neurons sis of positron emission tomography studies using 11C-2- projecting to the putamen. PSP is characterized by a more- beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane in profound and diffuse dopaminergic loss. patients with movement disorders. Nucl Med Commun We were able to show a significant correlation between 23:1047–1055 striatal uptake and UPDRS motor symptoms in PD, suggest- 7. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of 123 clinical diagnosis of idiopathic Parkinson’s disease: a clinic- ing that I-Ioflupane SPECT is also a specific marker of pathological study of 100 cases.
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