123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson?s disease, multiple system atrophy, and progressive supranuclear palsy

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson?s disease, multiple system atrophy, and progressive supranuclear palsy
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  123 I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT)uptake in patients with Parkinson’sdisease, multiple system atrophy, andprogressive supranuclear palsy  A. Antonini 1 (  ) • R. Benti 2 • R. De Notaris 1 S. Tesei 1 • A. Zecchinelli 1 • G. Sacilotto 1 N. Meucci 1 • M. Canesi 1 • C. Mariani 1 • G. Pezzoli 1 P. Gerundini 2 1 Centro per la malattia di Parkinson, Dipartimento diNeuroscienze, Istituti Clinici di Perfezionamento, Via Bignami 1,Milan, Italy 2 Medicina Nucleare IRCCS-Ospedale Maggiore, Milan, Italy Abstract We used SPECTand the tracer 123 I-Ioflupane tomeasure dopamine transporter (DAT) binding in the caudatenucleus and the putamen of 70 patients with Parkinson’s dis-ease (PD), 10 with multiple system atrophy (MSA-Ptype),and 10 with progressive supranuclear palsy (PSP). Data werecompared with 12 age-matched control subjects. We foundsignificant reductions in mean striatal values in all threeforms of parkinsonism. However, decrements were signifi-cantly greater in PSP(0.51±0.39,  p <0.01) compared withMSA-P(0.70±0.33) and PD (0.95±0.38). No differenceswere found between MSAand PD. Putamen/caudate ratioswere greater in PSP(0.83±0.12,  p <0.01) than in PD(0.51±0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and puta-men. Our results confirm that DATbinding can provide anaccurate and highly sensitive measure of dopamine degener-ation. PSPpatients may show a different pattern of neuronalloss compared with MSAand PD.Degenerative parkinsonian syndromes are characterized byprogressive loss of dopaminergic neurons in the substantianigra. Neuroimaging studies allow in vivo assessment of thenigro-striatal dopaminergic system and the extent of neu-ronal loss in these disorders. Tracers that bind selectively todopamine cells have been applied together with positronemission tomography (PET), and more recently single-pho-ton emission computed tomography (SPECT), for clinicaland research purposes. Historically, 18 F-fluorodopa/PETwasconsidered the gold standard for assessment of dopaminergicdenervation [1, 2]. There are, however, technical limitationsto the use of this tracer. Firstly, PETis available at few cen-ters. Secondly, it is likely that dopa-decarboxylase activity isupregulated early in the disease process, resulting in anunderestimation of dopaminergic neuronal loss. Thereforetracers that utilize the SPECTtechnique and bind selectivelyto the dopamine transporter (DAT) may be better suited andprovide more-accurate estimation of degeneration. Severaltracers that bind to DATand utilize SPECTare available;they are all cocaine derivatives. The most widely used are[ 123 I] β -CITand 123 I-Ioflupane ([ 123 I]FP-CIT) [3, 4]. Themain advantage of 123 I-Ioflupane is that a steady state allow-ing SPECTimaging is reached 3 h after a single bolus injec-tion of the radioligand, compared with the 18–24 h requiredfor [ 123 I] β -CIT. Therefore DATimaging with 123 I-Ioflupanecan be completed the same day.Several studies have demonstrated the usefulness of 123 I-Ioflupane SPECTimaging in the diagnosis of parkinsonism.Asensitivity of 97% has been reported for the identificationof nigrostriatal degeneration in Parkinson’s disease (PD) [5].Limited data are available on DATbinding in other degener-ative parkinsonisms, such as progressive supranuclear palsy(PSP) or multiple system atrophy (MSA) [6]. Patients and methods We studied DATbinding with 123 I-Ioflupane SPECTin 70 PDpatients (age 62±13 years, disease duration 5±4 years), 10 MSA-Ppatients (age 60±8 years, disease duration 4±2 years), and 10 PSPpatients (age 64±8 years, disease duration 4±3 years). UPDRSscores were obtained in all patients in “off” condition.Brain SPECTwas performed with a dedicated triple detectorgamma camera (Prism 3000, Philips) equipped with ultra-high-res-olution fan beam collimators. 123 I-Iofluopane (DATScan) (110–140MBq) was administered intravenously 30–40 min after thyroidblockade. SPECTstudies were acquired 3–4 h later and reconstruc-tion was performed by applying an iterative algorithm, followed bytridimensional filtering. Transaxial sections were attenuation cor-rected and reoriented with respect to the canthomeatal plane. Fouradjacent sections, including striatum and occipital cortex, weresummed 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.Iofluopane specific binding ratio was expressed as (striatal ROIcounts – occipital ROI counts)/(occipital ROI counts) and calculat-ed for the whole striatum, putamen, and caudate head of each hemi-sphere. We also calculated putamen/caudate ratios for each subject. Results We found significant decrements in DATbinding in the stria-tum of PD, MSA-P, and PSPpatients compared with healthycontrols. Mean striatal values were 0.95±0.38 in PD,0.70±0.33 in MSA, and 0.51±0.39 in PSP. Healthy controlshave striatal uptake values >1.7. An example of 123 I-IoflupaneSPECTin a control subject, a PD patient, and a PSPpatient is Neurol Sci (2003) 24:149–150DOI 10.1007/s10072-003-0103-5  shown in Fig. 1. We found that striatal values were signifi-cantly lower in PSPthan PD (  p <0.01). No differences werefound between MSA-Pand PD. Putamen/caudate ratios weregreater in PSP(0.83±0.12,  p <0.01) than in PD (0.51±0.11)and MSA-P(0.60±0.12). In PD patients we found a signifi-cant correlation with UPDRS motor scores (  p <0.001). Nocorrelation was found in the MSAand PSPcohorts. Discussion We found significant decrements of striatal DATin PD,MSA-P, and PSPpatients. We can confirm that 123 I-IoflupaneSPECTbinding is a sensitive measurement of the dopamin-ergic system in degenerative parkinsonsim. Moreover, wefound a different pattern of degeneration between PD andPSP. Asimilar finding has been previously reported with thetracer 18 F-fluorodopa in PSPpatients [2]. The greater decre-ments in the putamen than in the caudate nucleus in PDpatients is consistent with neuropathological data showingthat the bulk of nigral loss affects the dopaminergic neuronsprojecting to the putamen. PSPis characterized by a more-profound and diffuse dopaminergic loss.We were able to show a significant correlation betweenstriatal uptake and UPDRS motor symptoms in PD, suggest-ing that 123 I-Ioflupane SPECTis also a specific marker of disease progression. The absence of a significant correlationin other forms of parkinsonism was probably related to thefact that the majority of our MSAand PSPpatients hadalready marked disease at the time of SPECTscanning. 150 The differential diagnosis of different forms of parkin-sonism is not easy, particularly at an early stage. Although arecent report suggests that in a specialized tertiary centerdiagnostic accuracy can be as high as 90%, clinical patho-logical studies in the 1990s found the accuracy of clinicaldiagnosis to be only 76% [7], and the rate of misdiagnosis atearly stages of the disease may exceed this figure. In a recentcommunity based study conducted in a general practice, thediagnosis of clinically probable PD could only be confirmedin 53% of patients taking antiparkinsonian drugs [8]. Suchmisdiagnosis can lead to inappropriate management strate-gies that may include further unnecessary investigations.In conclusion, studies of the pre-synaptic dopaminergicsystem may prove clinically useful in assessing the presenceand extent of nigro-striatal loss in different forms of degen-erative parkinsonism. Additional neuroimaging investiga-tions, such as 123 I-IBZM for striatal dopamine receptors or1,STmagnetic resonance imaging, may help to characterizethese patients. The finding of a uniform and profound DATloss in the whole striatum seems to be specific to PSP. References 1.Antonini A, Vontobel P, Psylla M, Günther I, Maguire R,Missimer J, Leenders KL(1995) Complementary PETstudiesof the striatal dopaminergic system in Parkinson’s Disease.Arch Neurol 52:1183–11922.Brooks DJ, Ibanez V, Sawle GVet al (1990) Differing patternsof striatal 18F-dopa uptake in Parkinson’s disease, multiplesystem atrophy, and progressive supranuclear palsy. AnnNeurol 28:547–5553.Asenbaum S, Pirker W, Angelberger P, Bencsits G,Pruckmayer M, Brucke T(1998) [123I]beta-CITand SPECTin essential tremor and Parkinson’s disease. Journal NeuralTransm 105:1213–12284.Booij J, Andringa G, Rijks LJ et al (1997) 123I-FP-CITbindsto the dopamine transporter as assessed by biodistributionstudies in rats and SPECTstudies in MPTP-lesioned mon-keys. Synapse 27:183–1905.Benamer TS, Patterson J, Grosset DG et al (2000) Accuratedifferentiation of parkinsonism and essential tremor usingvisual assessment of [123I]-FP-CITSPECTimaging: the[123I]-FP-CITstudy group. Mov Disord 15:503–5106.Lucignani G, Gobbo C, Moresco RM, Antonini Aet al (2002)The feasibility of statistical parametric mapping for the analy-sis of positron emission tomography studies using 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane inpatients with movement disorders. Nucl Med Commun23:1047–10557.Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinic-pathological study of 100 cases. J Neurol NeurosurgPsychiatry 55:181–1848.Meara J, Bhowmick BK, Hobson P(1999) Accuracy of diag-nosis in patients with presumed Parkinson’s disease. AgeAging 28:99–102 Fig. 1 123 I-Ioflupane SPECTin a control subject, a PD patient, anda PSPpatient Healthy controlParkinson’s diseaseProgressive supranuclear palsy
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