Striatal dopamine function in a family with multiple SCA-3 phenotypes

We present single photon emission computed tomography (SPECT) studies using 123IFP-CIT (DAT scan) and 123I-IBZM imaging, performed on four members of a family with genetically proven spinocerebellar ataxia type 3 (SCA-3). DAT scan showed significant asymmetric decreased binding in the striatum in the two members with predominant parkinsonian phenotype, with mild and symmetric decreased binding in the member with the cerebellar phenotype, and normal in the asymptomatic member. The IBZM SPECT studies showed mild and asymmetrical reduction of the striatal dopamine D2 receptor density (parkinsonian members). SCA-3 can present with a levodopa responsive parkinsonism phenotype, and an abnormal DAT scan showing predominant impairment of presynaptic dopamine function.     

Clinical and [99mTc]TRODAT-1/[123I]IBZM SPECT imaging findings in dopa-responsive dystonia

We report the clinical and dopamine transporter/D2 receptor single-photon emission computed tomographic (SPECT) imaging findings in a 39-year-old woman with a 24-year history of dopa-responsive dystonia (DRD). The SPECT imaging of the dopamine transporter with [(99m)Tc]TRODAT-1 is helpful in differentiating DRD from early-onset idiopathic parkinsonism. In the later clinical course, the [(123)I]IBZM SPECT is also helpful in differentiating these two conditions. The patient showed a dramatic and sustained response to levodopa, and needed a smaller dose of levodopa for symptom control in the later course.     

(123I) beta-CIT and single-photon emission computed tomographic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis

BACKGROUND: The diagnosis of Parkinson disease is currently based on clinical evaluation. Functional neuroimaging using (123I) beta-carboxymethyoxy-3-beta-(4-iodophenyl) tropane (CIT) and single-photon emission computed tomography (SPECT) provides information on the integrity of the dopaminergic system in vivo and is a promising diagnostic tool in early Parkinson disease. OBJECTIVE: To evaluate the diagnostic accuracy of dopamine transporter imaging using (123I)beta-CIT in patients with suspected parkinsonian syndrome (PS). DESIGN: Community neurologists referred patients with suspected PS for imaging evaluation. Clinical diagnoses (positive PS or negative PS) were provided by the community neurologists and 2 movement disorder experts. We performed (123I)beta-CIT and SPECT imaging, and imaging diagnoses of positive PS or negative PS were assigned. A 6-month follow-up clinical diagnosis was assigned by a movement disorder expert blind to the imaging data, which represented the "gold standard" diagnosis for the study. RESULTS: Thirty-five patients with suspected PS were referred. Diagnoses in question included essential tremor, psychogenic parkinsonism, drug-induced parkinsonism, primary dystonia, and unspecified gait disorder. Comparing the community neurologist's diagnoses at referral with the gold standard diagnosis, there was dis agreement in 25.7% (sensitivity, 0.92; specificity, 0.30). Comparing the quantitative imaging diagnoses with the gold standard, there was disagreement in 8.6% (sensitivity, 0.92; specificity, 1.00). CONCLUSION: Performing (123I)beta-CIT and SPECT imaging at baseline appears to be a useful diagnostic tool to detect patients thought to have PS at baseline but who, after follow-up, do not have PS.     

Decreased striatal dopamine transporter binding in a patient with extrapontine myelinolysis.

We describe the case of a 61-year-old woman who developed extrapontine myelinolysis (EPM) with parkinsonism. Decreased striatal dopamine transporter binding assessed by [(123)I]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane and single photon emission computed tomography ([(123)I]IPT) SPECT) were observed in the patient, suggesting that osmotic injury causes the demyelination of nigrostriatal dopaminergic neurons and that such injury may be involved in the pathogenesis of EPM with parkinsonism.     

Dopamine transporter loss and clinical changes in MPTP-lesioned primates

Single photon emission computed tomography (SPECT) and the dopamine (DA) transporter tracer, 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT), were used to determine DA transporter density in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-lesioned monkeys with varying degrees of parkinsonism. The clinical stage of parkinsonism corresponded to SPECT measures of striatal DA transporter density suggesting that more severe parkinsonism was associated with a greater degree of dopaminergic terminal degeneration. These findings are similar to those reported earlier using positron emission tomography (PET) and the DA metabolism tracer, 6-[18F]fluoro-L-m-tyrosine (FMT), indicating that both are good methods for evaluating nigrostriatal degeneration in MPTP primate models.     

Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]beta-CIT SPECT analysis

BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. OBJECTIVE: To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING: Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.     

Subclinical nigrostriatal dopaminergic denervation in the cerebellar subtype of multiple system atrophy (MSA-C)

Nigrostriatal involvement is considered an additional feature in the new consensus criteria for the diagnosis of the cerebellar variant of multiple system atrophy (MSA-C). However, so far, only a few studies, which include a relative small number of patients, give support to this criterion. Our objective was to assess nigrostriatal dopaminergic innervation in patients with MSA-C without parkinsonism by use of dopamine transporter single photon emission computed tomography (DAT SPECT). Thirteen patients that fulfilled criteria for possible or probable MSA-C and presented no parkinsonian signs, and 12 age-matched healthy controls underwent (¹²³I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([¹²³I]FP-CIT) SPECT. Patients were also evaluated through the Unified Multiple System Atrophy Rating Scale (UMSARS) and brain magnetic resonance imaging (MRI). The mean duration of the cerebellar syndrome was 3.8 ± 1.7 years. DAT SPECT showed a significant decrease of striatal [¹²³I]FP-CIT uptake ratios in patients (p < 0.001). Radiotracer uptake reduction was 21% in the entire striatum, 19% in putamen, and 24% in caudate nuclei. Striatal binding ratios were within the normal range in 3 patients. We did not find correlation between striatal uptake and disease duration, age of patients, UMSARS-II score, and pontine diameter. [¹²³I]FP-CIT SPECT shows that most but not all MSA-C patients without parkinsonism have subclinical nigrostriatal dopaminergic denervation which is not related to disease duration, cerebellar dysfunction, or pontine atrophy.     

123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson's disease.

Parkinsonism in patients taking neuroleptic medications might be induced by dopamine receptor blockade alone or by dopamine blockade with nigrostriatal dysfunction. The differentiation between Parkinson's disease (PD) and drug-induced parkinsonism (DIP) is difficult to assess on clinical grounds alone. In this study, we have evaluated the clinical characteristics and striatal binding of (123)I-FP-CIT (N-omega-fluoropropyl-2beta-carboxymethoxy-3beta-{4-iodophenyl}tropane) in patients who developed DIP. A total of 20 patients (mean age, 62 +/- 13 years) who developed parkinsonism while on neuroleptic agents and 10 age-matched controls were enrolled. [123]-FP-CIT single-photon emission computed tomography (SPECT) was performed in all subjects. Neurological assessment was performed with the Motor part of the Unified Parkinson's Disease Rating Scale. [123]-FP-CIT binding of the entire striatum, caudate, and putamen was calculated. Patients were divided into two subgroups according to SPECT results for comparison of clinical characteristics. There were 9 patients who had normal scans and 11 who showed significantly diminished striatal binding, suggesting degeneration of the nigrostriatal system. Subanalyses of abnormal scans revealed significantly diminished binding in the caudate (P < 0.001 for right and left caudate) and putamen (P = 0.002 and P < 0.05 for right and left putamen, respectively). There were no differences in clinical features between patients with normal and abnormal scans. Symptoms included asymmetric tremor, bradykinesia, and rigidity in both groups. Freezing gait was present in two patients with normal scans. These results indicate that DIP is clinically indistinguishable from PD. Brain imaging with FP-CIT helps to determine whether DIP is entirely drug-induced or an exacerbation of subclinical PD.     

A Case of Biopsy-proven Early-onset Alzheimer's Disease with Hemiparkinsonism

Patients with dementia and concomitant parkinsonism are frequently encountered in the elderly population. When it comes to young adults, however, coexistence of Alzheimer''s disease (AD) and Parkinson''s disease (PD) is rare. We described a case of 47-year old man with presenile onset dementia associated with hemiparkinsonism involving the right extremities. Brain biopsy showed neurofibrillary tangles and neuritic plaques, compatible with Alzheimer''s disease. Iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) SPECT, dopamine transporter imaging, revealed a decreased uptake in both basal ganglia, more severe on the left side, particularly the caudal putamen, which is consistent with the finding of idiopathic Parkinson''s disease. This case is unique in that damage on the nigrostriatal dopaminergic system in a patient with Alzheimer''s disease was demonstrated by a functional neuroimaging study and that early-onset AD and early-onset PD, two rare conditions, coexist in the same individual.     

Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes.

Imaging with (123)I-Ioflupane single-photon emission computed tomography (SPECT) is a marker of nigrostriatal neuronal integrity, allowing differentiation of parkinsonism with loss of dopaminergic terminals (presynaptic Parkinson syndrome [PS]) from parkinsonism without nigrostriatal degeneration. This study assessed SPECT imaging in 118 patients with clinically uncertain parkinsonian syndromes (CUPS). In 36% of patients with presynaptic PS and 54% with nonpresynaptic PS, imaging results were not consistent with the initial diagnosis. After imaging, diagnosis was changed in 52% of patients. All patients with a final diagnosis of presynaptic PS had an abnormal image, whereas 94% of patients with nonpresynaptic PS had a normal scan. Imaging increased confidence in diagnosis, leading to changes in clinical management in 72% of patients. Consequently, visual assessment of (123)I-Ioflupane SPECT may have a significant impact on the clinical management of CUPS patients.     

123I]-FP-CIT-SPECT demonstrates dopaminergic deficit in orthostatic tremor

There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.     

Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study

OBJECTIVE: In vivo imaging studies have revealed deregulated presynaptic or postsynaptic function of the midbrain dopaminergic system in patients with schizophrenia. To further delineate the neuropathological involvement of the presynaptic and postsynaptic dopamine neurons in schizophrenia, the authors examined brain D(2)-family receptor and dopamine transporter binding simultaneously in patients with drug-naive schizophrenia using the dual-isotope single photon emission computed tomography (SPECT) imaging technique. METHOD: Eleven patients with schizophrenia and 12 healthy comparison subjects were recruited. Striatal dopamine D(2)/D(3) receptor was measured with SPECT and [(123)I]iodobenzamide ([(123)I]IBZM), while dopamine transporter was measured with SPECT and [(99m)Tc]TRODAT-1. RESULTS: Striatal D(2)/D(3) receptor and dopamine transporter binding were unaltered in these drug-naive patients with schizophrenia. Nonetheless, D(2)/D(3) receptor binding measures were positively correlated with dopamine transporter binding measures in these patients but not in the comparison subjects. CONCLUSIONS: The associated presynaptic and postsynaptic disturbances of midbrain dopamine neurons could be clinically relevant in drug-naive patients with schizophrenia.     

Thiethylperazine-induced parkinsonism: in vivo demonstration of dopamine D2 receptors blockade

Thiethylperazine (Torecan) is a piperazine phenothiazine employed to relieve vertigo. Its use may be associated with extrapyramidal side effects (dystonia, akathisia, tardive dyskinesia) (Sulkava, 1984), but parkinsonism has rarely been described. We describe a woman who, 1 month after the onset of thiethylperazine treatment, developed parkinsonism that disappeared 2 months after withdrawal of the drug. However, cerebral single-photon emission computed tomography (SPECT) with the dopamine (DA) D2 receptors ligand 123I-iodobenzamide (123I-IBZM) revealed a persistent reduced DA D2 receptors activity (by 45%) in the basal ganglia (BG), which may be clinically not effective.     

Preclinical impairment of the striatal dopamine transporter system in sporadic olivopontocerebellar atrophy: studied with [(123)I]beta-CIT and SPECT

We investigated whether the dopamine (DA) transporter system is impaired in sporadic olivopontocerebellar atrophy (sOPCA) patients without clinical parkinsonism using the DA transporter radiotracer [(123)I]beta-CIT [2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane] and single-photon emission computed tomography (SPECT). SPECT scans were acquired in 9 patients with sOPCA, 7 multiple system atrophy (MSA) patients with parkinsonism (MSA-P), and 7 age-matched healthy controls 20-24 h after the intravenous injection of [(123)I]beta-CIT. [(123)I]beta-CIT-specific binding in the striatum was determined as the radioactivity ratio of the striatum to the occipital cortex (specific binding ratio, SBR). In patients with sOPCA and MSA-P, SBRs in the right and left striatum and the mean SBR were significantly lower than those in controls (p < 0.05). The mean SBRs in patients with sOPCA and MSA-P were reduced to 69.0 and 60.7% of the control mean, respectively. However, there was no significant difference in SBRs between sOPCA and MSA-P patients. In sOPCA patients, the mean SBR was significantly correlated with the score of the clinical cerebellar function scale (r = -0.670, p = 0.024). These results indicate that even in the absence of clinical parkinsonism, the striatal dopaminergic system may be impaired in sOPCA. The DA transporter loss in sOPCA serves as another clue for sOPCA being a part of the spectrum of MSA.     

Dopamine transporter density measured by [123I]β-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia

The clinical distinction between dopa-responsive dystonia (DRD) and juvenile Parkinson's disease (JPD) can pose a diagnostic challenge. Both conditions are dopa responsive. However, long-term L-dopa benefit is very different between the two. The difference in the prognosis is due to presence or absence of nigral cell loss. In JPD, there is degenerative nigral cell loss, wherease there are enzymatic defects in dopamine synthesis without cell loss in DRD. Mutations have been found in the GTP cyclohydrolase I (GCH-I) and tyrosine hydroxylase genes in DRD. As the discovered mutations are multiple and more are expected to be found, it is difficult to confirm or exclude DRD by mutation studies. Measurement of cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH-I gene but not from mutations in tyrosine hydroxylase. The dopamine transporter (DAT) is a protein in the dopaminergic nerve terminals. (1R)-2β-Carbomethoxy-3β-(4-[¹²³I]iodophenyl)tropane ([¹²³I]β-CIT) is a ligand for the DAT, and it was shown to be a useful nuclear imaging marker for neurons that degenerate in Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral cell loss in a postmortem study, we predicted that the DAT measured in vivo by nuclear imaging will be normal in DRD and will differentiate DRD from JPD. Therefore, we performed [¹²³I]β-CIT single-photon emission computed tomography ([¹²³I]β-CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined whether DAT imaging can differentiate DRD from PD and JPD. We then examined whether DAT imaging can provide a screening tool for molecular genetic studies, by studying mutations in the candidate gene GCH-I and measuring CSF neopterin. Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on early-onset foot dystonia and progressive parkinsonism beginnig at ages 7 to 12. All patients were functioning normally on L-dopa 100 to 250 mg/day for up to 8 years. SPECT imaging was obtained after intravenous injection of [¹²³I]β-CIT; 15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease controls. [¹²³I]β-CIT striatal binding was normal in DRD, whereas it was markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation in the GCH-I gene in one family. No mutation was found in the other family or in the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients. [¹²³I]β-CIT SPECT is a sensitive method for probing the integrity of nitegrity of nigrostriatal dopaminergic nerve terminals. A normal striatal DAT in a parkinsonian patient is evidence for a nondegenerative cause of parkinsonism and differentiates DRD from JPD. Finding a new mutation in one family and failure to demonstrate mutations in the putative gene in other cases supports the usefulness of DAT imaging in diagnosing DRD.     

Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome

Fourteen drug-naive and 11 levodopa-treated patients with idiopathic restless legs syndrome (RLS), and 10 controls age-matched to each RLS group separately were examined with polysomnography (PSG), [(123)I]-(N)-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ((123)I-IPT) SPECT, and [(123)I]-(S)-2-hydroxy-3-iodo-6-methoxy-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide ((123)I-IBZM) SPECT. Drug-naive and levodopa-treated patients with RLS and controls showed similar striatal dopamine transporter and dopamine D(2)-receptor binding, the latter declining with age. The authors conclude that striatal dopamine transporter and receptor density is normal in drug-naive and levodopa-treated patients with RLS.     

Dravet syndrome with parkinsonian symptoms and intact dopaminergic neurons: A case report

IntroductionDravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms.Case reportCase 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of ¹²³I–N–ω–fluoropropyl–2β–carbomethoxy–3β–(4–iodophenyl) nortropane (¹²³I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms.DiscussionThe normal DAT SPECT and ¹²³I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.     

Cerebrotendinous xanthomatosis patients with and without parkinsonism: Clinical characteristics and neuroimaging findings

Parkinsonism in cerebrotendinous xanthomatosis (CTX) is rare. There are no published studies with imaging findings of dopamine transporter using ^99mTc‐[2‐[[2‐[[[3‐(4‐chlorophenyl)‐8‐methyl‐8‐azabicyclo [3,2,1] oct‐2‐yl] methyl] (2‐mercaptoethyl) amino] ethyl] amino]‐ethanethiolato(3‐)‐N2,N2,S2,S2]oxo‐[1R‐(exo‐exo)] (^99mTc‐TRODAT‐1) SPECT in CTX patients. This report is on the clinical details of five genetically‐proven CTX patients (two with and three without parkinsonism). Imaging findings using cranial magnetic resonance (MR) imaging and ^99mTc‐TRODAT‐1 SPECT are also shown. Clinical correlation of neuroimaging findings and clinical presentations was made. A literature review of the clinical and neuroimaging features of eight CTX patients with parkinsonism reported in the English literature is also presented. The parkinsonian features of our two cases and the other eight reported cases occurred before the age of 50 years. The MR imaging study showed variable findings, in which, besides the common diffuse cerebral and cerebellar white matter lesions shown in CTX, several focal brain lesions were also noted. Of the focal lesions, substantia nigra abnormalities were seen only in the two cases with parkinsonism. The ^99mTc‐TRODAT‐1 SPECT study showed different degrees of unilateral or bilateral abnormalities in the striatal binding in both visual and semiquantitative assessments. parkinsonism can be one of the neurologic presentations of CTX. Even though abnormal findings of the substantia nigra were detected in both of our CTX patients with parkinsonism, basal ganglion lesions have not been uniformly described in MR imaging findings of reported CTX patients with parkinsonism. ^99mTc‐TRODAT‐1 SPECT study can be of value in the detection of striatal involvement, and the study results also suggest pre‐synaptic dopamine neuron involvement in CTX patients with parkinsonism. © 2010 Movement Disorder Society     

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: A 3‐year European multicenter study with repeat [123I]FP‐CIT SPECT

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [¹²³I]FP‐CIT (DaTSCAN?, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video‐recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on‐site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [¹²³I]FP‐CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter‐reader agreement for rating scans as normal or abnormal was high (Cohen's = 0.94–0.97). © 2008 Movement Disorder Society     

Visualizing dopamine transporter integrity with iodine-123-FP-CIT SPECT in combination with high resolution MRI in the brain of the common marmoset monkey

Considerable progress has been made in small animal single photon emission computed tomography (SPECT) imaging in the field of Parkinson's disease. In preclinical research, there is an increasing demand for in vivo imaging techniques to apply to animal models. Here, we report the first protocol for dopamine transporter (DAT) SPECT in common marmosets using the radioligand (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ((123)I-FP-CIT). Serial SPECT images were obtained on an upgraded clinical scanner to determine the distribution kinetics of (123)I-FP-CIT in the marmoset brain. After intravenous injection of approximately 60MBq of the radiotracer (123)I-FP-CIT, stable and specific striatal uptake was observed for at least 4h. Analysis of plasma samples showed rapid disappearance of the radiotracer from blood plasma within a few minutes after application, with activity declining to 4.1% of the administered activity. Structural magnetic resonance imaging (MRI) at 400μm resolution provided the details of the underlying anatomy. In a marmoset model of Parkinson's disease, which was generated by unilateral injections of 6-hydroxydopamine (6-OHDA) into the nigro-striatal projection pathway, complete loss of striatal DAT binding in combination with behavioral deficits was observed. The presented study demonstrates that (123)I-FP-CIT SPECT is a suitable tool to investigate DAT integrity in preclinical studies on common marmosets.