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.     

Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A 123I‐FP‐CIT SPECT study

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with ¹²³I‐labeled ligand N‐δ‐(fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)tropene (¹²³I‐FP‐CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, ¹²³I‐FP‐CIT imaging was performed in 18 well‐characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. Theseresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB. © 2009 Movement Disorder Society     

Parkinsonism and essential tremor in a family with pseudo-dominant inheritance of PARK2: an FP-CIT SPECT study.

We report a family with 5 affected individuals manifesting either essential tremor (ET), Parkinsonism, or both, consistent with pseudo-dominant inheritance of PARK2. Two homozygotes presented postural and kinetic tremor several years before the onset of Parkinsonism. Postural and kinetic tremor mimicking ET was the only feature in 1 homozygous and 2 heterozygous carriers of the mutation. Striatal dopamine transporter density was reduced in accordance with phenotype and number of mutated alleles. In 3 homozygotes and 1 heterozygote, a 2-year follow-up single photon emission computed tomography suggested no progression of nigrostriatal deficit.     

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.     

Cognitive‐nigrostriatal relationships in de novo,drug‐naïve Parkinson's disease patients: A [I‐123]FP‐CIT SPECT study

To unveil cognitive‐nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug‐naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I‐123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys‐executive (NPS‐EX), a visuospatial (NPS‐VS), a verbal memory (NPS‐VM), and a “mixed” (NPD‐MIX) factor. In PD group, there were inverse correlations between UPDRS‐III score and both NPS‐VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS‐EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS‐EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS‐III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro‐caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro‐putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies. © 2010 Movement Disorder Society     

Psychogenic parkinsonism: a combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy.

We evaluated the concordance between independent clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations as a staged procedure for an accurate diagnosis in 9 patients referred with a diagnosis of suspected psychogenic parkinsonism. Three patients were reclassified as pure psychogenic parkinsonism (PP), 6 with a form of combined psychogenic parkinsonism and Parkinson's disease (PP + PD), and none with pure Parkinson's disease (PD). Electrophysiological recordings showed the characteristics of psychogenic tremor in 5 of 7 patients with tremor. In two of these 5, PD tremor was also recorded. SPECT scan results were abnormal in five of 9 patients. In one case of clinically suspected PP + PD, SPECT scan results were normal. Long-term follow-up supported the final diagnosis of PP (initial clinical misdiagnosis). Electrophysiology contributes to the clinical diagnosis of psychogenic tremor and may help confirm associated organic PD tremor. [(123)I]-FP-CIT SPECT is a robust test to ascertain dopaminergic denervation and increase the confidence of the clinical and electrophysiological diagnosis of associated PD. A combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy in order to distinguish PP from PP + PD.     

Abnormalities of dopaminergic neurotransmission in SCA2: A combined 123I‐βCIT and 123I‐IBZM SPECT study

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and β‐CIT as well as IBZM. Age‐matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of β‐CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level. © 2004 Movement Disorder Society     

[123I]FP‐CIT SPET imaging in drug‐induced Parkinsonism

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug‐induced parkinsonism (DIP). We performed [¹²³I]FP‐CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS‐III was used to assess clinical severity. Twenty‐six age‐ and sex‐matched healthy subjects served as control group. Putamen [¹²³I]FP‐CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco‐linguo‐masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals. © 2008 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     

Kinetic modeling and occupancy measures of the norepinephrine transporters in baboons using single photon emission computed tomography with 123I‐INER

This study aims to investigate the pharmacokinetics of a recently developed radiotracer for imaging of the norepinephrine transporter (NET) in baboon brain, ¹²³I‐INER, using single photon emission computed tomography (SPECT). In addition, it also aims to determine NET occupancy by atomoxetine and reboxetine, two selective norepinephrine reuptake inhibitors, using ¹²³I‐INER in baboons. Baseline and preblocking studies with a high dose of atomoxetine (0.85 mg/kg) were conducted in three baboons using SPECT with ¹²³I‐INER administered as a bolus. Kinetic modeling analysis was investigated for different models, namely invasive and reference tissue models. Bolus plus constant infusion experiments with displacement at equilibrium using six different doses of atomoxetine (0.03–0.85 mg/kg) and four different doses of reboxetine (0.5–3.0 mg/kg) were carried out in several baboons to obtain occupancy measurements as a function of dose for the two NET selective drugs. Results showed that reference tissue models can be used to estimate binding potential values and occupancy measures of ¹²³I‐INER in different brain regions. In addition, the apparent volume of distribution was estimated by dividing concentration in tissue by the concentration in blood at 3 hours postinjection. After administration of atomoxetine or reboxetine, a dose‐dependent occupancy was observed in brain regions known to contain high densities of NET. In conclusion, pharmacokinetic properties of ¹²³I‐INER were successfully described, and obtained results may be used to simplify future data acquisition and image processing. Dose‐dependent NET occupancy for two selective norepinephrine reuptake inhibitors was successfully measured in vivo in baboon brain using SPECT and ¹²³I‐INER. Synapse, 2013. © 2012 Wiley Periodicals, Inc.