Investigating dopaminergic neurotransmission with 123I-FP-CIT SPECT: comparability of modern SPECT systems.

With (123)I-labeled N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl)nortropane (FP-CIT) SPECT increasingly gaining access into routine patient care, the comparability of the results of different SPECT systems in the quantification of receptor binding is important for accurate clinical decision making and the translation of imaging results between institutions (e.g., as part of multicenter therapy trials). METHODS: In a series of studies using phantoms (containing target cylinders of 2- and 2.8-cm diameter) and (123)I-FP-CIT patient studies (n = 49), we compared target-to-background (T/BG) and (123)I-FP-CIT striatal uptake ratios recovered by a conventional triple-head SPECT system and a dedicated high-resolution brain SPECT system. All patient studies were acquired on both SPECT systems successively (<15-min interscan gap) using a single-injection protocol (group A [n = 20] was first scanned on the triple-head SPECT system, and group B [n = 29] was first scanned on the dedicated brain SPECT system). RESULTS: In phantom studies, the T/BG ratios recovered by both systems correlated strongly with the true T/BG ratios (R(2) > 0.96), with the linear regression slopes being 0.86-1.17 and 0.41-0.52 (less steep for smaller target size and lower T/BG ratios) for the dedicated brain SPECT and the triple-head SPECT system, respectively. Although both systems yielded markedly different results, they showed a high linear correlation with each other (R(2) > 0.95, no significant effect from target size). In (123)I-FP-CIT patient studies, a similar linear intersystem correlation was found (R(2) [A/B] = 0.79/0.80, 0.52/0.68, and 0.83/0.85 for the uptake ratios of the striatum, caudate, and putamen, respectively, to the occipital reference region). CONCLUSION: A linear transformation of striatal uptake ratios between different SPECT systems appears to be achievable for ligands such as (123)I-FP-CIT. An evaluation is needed of whether the present method can do this with sufficient accuracy for clinical purposes or whether methodologic adaptations are necessary. Proper study timing has to be ensured.     

123I-FP-CIT in progressive supranuclear palsy and in Parkinson's disease: a SPECT semiquantitative study

BACKGROUND AND AIM: It is still debated whether or not I-FP-CIT single photon emission computerized tomography (SPECT) is able to differentiate between Parkinson's disease and progressive supranuclear palsy (PSP). Our aim was to use SPECT semiquantitative analysis to assess the capacity of I-FP-CIT to characterize Parkinson's disease versus PSP. PATIENTS AND METHODS: Twenty-one Parkinson's disease patients, 15 disease duration- and age-matched PSP patients and 20 age-matched healthy controls were included in this study. SPECT imaging was always performed at 4 h post-injection. The ratios of striatal (S) to non-specific occipital (O) binding for the entire striatum (S/O), caudate nuclei (C/O), putamina (P/O) were calculated in both the basal ganglia. The asymmetric index (AI) for the whole striatum was also calculated for Parkinson's disease and PSP. RESULTS: Compared to healthy controls, S/O, C/O and P/O were significantly reduced (P<0.001) both in Parkinson's disease (-46%, -43%, -49%, contralaterally to the most affected side; -41%, -37%, -41%, ipsilaterally) and in PSP (-58%, -57%, -59%, contralaterally; -58%, -57%, -59%, ipsilaterally). S/O, C/O and P/O ratio values were significantly (P<0.001) lower in PSP patients when compared to Parkinson's disease group. The asymmetric index (AI) was significantly higher (P<0.001) in Parkinson's disease than in PSP (AI: 23.6%+/-15.07% vs. 9.66%+/-5.83), but with an overlap between the two groups. CONCLUSION: Our results confirm that I-FP-CIT SPECT is clinically useful for detecting nigrostriatal degeneration both in Parkinson's disease and PSP. Moreover, in our series, semiquantitative analysis using I-FP-CIT SPECT allowed Parkinson's disease and PSP to be discriminated because PSP patients presented a more severe and symmetric dopamine transporter loss, and the results for S/O were more accurate.     

Clinical features and 123I-FP-CIT SPECT imaging in drug-induced parkinsonism and Parkinson’s disease

Purpose  

To determine clinical predictors and accuracy of ¹²³I-FP-CIT SPECT imaging in the differentiation of drug-induced parkinsonism (DIP) and Parkinson’s disease (PD).     

Clinical evaluation of Parkinson's disease using 123I-IMP SPECT

N-isopropyl-p[123I]iodoamphetamine (123I-IMP) SPECT and regional cerebral blood flow (rCBF) studies were performed in 20 patients with Parkinson's disease (PD) and 8 normal subjects. RCBF was measured by the arterial blood sampling method which used the microsphere model. We analyzed seven factors which might be related to the rCBF in PD, i.e., age, stage, duration of the disease, cerebral atrophy, severity of dementia, laterality of symptoms and motor disability score (MDS; the degree of akinesia, rigidity, tremor, gait disturbance, freezing and pulsion sign). Compared with normal subjects, global CBF (supratentorial mean rCBF) was reduced 21.8% in PD. In particular, rCBF in the basal ganglia and that of frontal cortex were reduced 25.3%, 24.8%, respectively. Distribution patterns of rCBF in PD were almost as same as those in normals except for cerebellum. The reduction of both rCBFs in the basal ganglia and parietal cortex significantly correlated with MDS (p less than 0.05, respectively). Especially, akinesia was closely correlated to the reduction of rCBF in the parietal cortex (p less than 0.02). Moreover, we observed a significant relationship between cerebral atrophy and reduction of rCBF in each region except for cerebellum. However, there was no significant correlation between the severity of dementia and reduction of rCBF, even in the frontal cortex or parietal cortex. These data show that the severity of dementia in PD may be connected with other factors except for rCBF. 123I-IMP SPECT study is a useful method for clinical evaluation of PD.     

Practical benefit of [123I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson's disease

Loss of striatal dopamine (DA) transporters in Parkinson's disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [¹²³I]-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20–30 h following the injection of [¹²³I]-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand,N--fluoropropyl-2-carbomethoxy-3-(4-iodophenyl)tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [¹²³I]FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [¹²³I]-CIT (24 h following injection) and one with [¹²³I]FP-CIT (3 h following injection). The ratios of specific to non-specific [¹²³I]FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [¹²³I]-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [¹²³I]FP-CIT seems as good as [¹²³I]-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [¹²³I]FP-CIT are a clear advantage.     

123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism.

The purpose of our study was to prospectively evaluate the striatal uptake of 123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP). METHODS: Twenty consecutive patients who developed VP in the course of CVD were prospectively enrolled in the study. All patients had CT evidence of CVD (17 patients had lacunar infarcts, 3 patients had territorial strokes). The clinical stage of the patients was assessed using the Hoehn and Yahr scale, and the severity of the symptoms was measured using the Unified Parkinson's Disease Rating Scale score. Ten age-matched subjects were used as controls. SPECT was performed 180 min after injection of 185 MBq 123I-FP-CIT using a dual-head gamma-camera. The ratio of the mean specific-to-nonspecific striatal binding for the entire striatum, caudate, and putamen was calculated in all patients and compared with that of controls. Putamen-to-caudate binding ratios were compared as well. The response to therapy was compared between patients with normal and abnormal 123I-FP-CIT binding. RESULTS: No correlation was found between any of the clinical variables and response to therapy in patients with VP. Nine patients had normal striatal 123I-FP-CIT binding with no significant differences in striatal or subregional binding ratios compared with those of the controls. In contrast, 11 patients had significantly diminished striatal binding compared with that of controls (P < 0.001). Subanalyses showed significantly decreased binding in the caudate (P < 0.04 and P < 0.01 for the right and left caudate, respectively), diminished binding in the putamen (P < 0.04 and P < 0.01 for the right and left putamen, respectively), and a decreased putamen-to-caudate ratio on the right side (P < 0.001). The latter ratio was not significant on the left. Two of the 3 patients with territorial strokes had significantly diminished striatal 123I-FP-CIT binding in the hemisphere contralateral to the CT lesion. All 9 patients with normal scan findings had a poor response to L-dopa. Six of 11 patients with abnormal studies had no response to L-dopa, whereas 5 patients had a good response (P < 0.03). CONCLUSION: The diagnosis of VP cannot be accurately confirmed on the basis of clinical features alone because CVD may alter the typical presentation of PD. Functional imaging with 123I-FP-CIT is highly recommended in patients with CVD who develop symptoms of VP to confirm or exclude the existence of nigrostriatal dopaminergic degeneration. Identifying a subset of patients with reduced 123I-FP-CIT binding in the striatum is important for better treatment selection.     

One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123I]FPCIT SPECT.

Parkinson's disease is characterized by degeneration of dopaminergic neurons, resulting in loss of dopamine transporters in the striatum. Recently, the tracer 1231-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane (FPCIT) was developed for imaging dopamine transporters with SPECT. The purpose of this study was to develop an [123I]FPCIT SPECT protocol for routine clinical studies. METHODS: We examined the time course of [123I]FPCIT binding to dopamine transporters in 10 healthy volunteers and 19 patients with Parkinson's disease. RESULTS: We found that the time of peak specific striatal [123I]FPCIT binding was highly varied among subjects, but specific binding peaked in all controls and patients within 3 h postinjection. Between 3 and 6 h, the ratio of specific-to-nonspecific striatal [123I]FPCIT binding was stable in both groups, although, as expected, it was significantly lower in patients. In the patients, [123I]FPCIT binding in the putamen was lower than in the caudate nucleus, and contralateral striatal binding was significantly lower than ipsilateral striatal binding. The subgroup of patients with hemi-Parkinson's disease showed loss of striatal dopamine transporters, even on the ipsilateral side. CONCLUSION: For routine clinical [123I]FPCIT SPECT studies, we recommend imaging at a single time point, between 3 and 6 h postinjection, and using a tissue ratio as the outcome measure. The [123I]FPCIT SPECT technique is sensitive enough to distinguish control subjects from patients with Parkinson's disease, even at an early stage of the disease.     

123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis

Annals of Nuclear Medicine - 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter...     

Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.

In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease process. The integrity of 5-HT transporters was assessed in PD patients with SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta-CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters. METHODS: Forty-five PD patients at relatively early stages (mean Hoehn-Yahr stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15 scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio (R(A)) method, and a modified graphic method that derives the ratio of ligand distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is equivalent to k(3)/k(4), was measured using the images acquired at 24 h after tracer injection. All measures were derived using the cerebellum as the reference region. RESULTS: In control subjects, the (123)I-beta-CIT activity in the midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and cerebellar activity were not significantly different from those in control subjects. None of midbrain R(PE), R(A), and R(V) was significantly different between control subjects and PD patients, whereas striatal V(3)" was bilaterally reduced in all patients, being 32% lower than that of the control subjects (P = 0.002). In PD patients, none of the midbrain outcome measures was significantly correlated with either striatal V(3)" or motor or nonmotor symptom ratings, including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale scores. When the studies of 7 PD patients with depression were analyzed separately, none of the midbrain outcome measures in these patients either was different significantly from control values or correlated with the Hamilton Depression Rating Scale score. CONCLUSION: These results suggest that DA and 5-HT transporters are differentially affected in PD, and 5-HT transporters in the midbrain region may not be affected in relatively early stages of PD. Alternatively, 5-HT transporters in the remaining neurons may be upregulated, thus raising the midbrain 5-HT transporter density to almost normal levels.     

Dopamine transporter SPECT in patients with Parkinson's disease

The major neuropathological feature in Parkinson's disease (PD) is severe degeneration of the dopamine (DA) neurons in the substantia nigra. Dopamine transporter (DAT) is an important protein in the regulation of DA neurotransmission. It has been reported that PD patients show a loss of DAT in striatum. We report here the findings of single photon emission computed tomography (SPECT) of the DAT with 2 beta-carboxymethoxy-3 beta-(4[123I]iodophenyl)tropane ([123I] beta-CIT) to investigate striatal DAT in 10 patients with PD, one patient with vascular parkinsonism (VP), and one patient with dystonia syndrome. Patients were evaluated using the Webster rating scale. Specific/nondisplaceable striatal binding ratio (V3") was obtained in each case. In PD patients, the uptake of [123I] beta-CIT was reduced, especially in the tail of putamen compared with caudate nucleus. Even in the early stage of PD, the uptake of beta-CIT was reduced not only in the severely affected side, but also in the mildly disturbed side of the brain. Putamen caudate ratio was generally low in PD patients. In VP patient, the uptake was reduced, but putamen caudate ratio was not decreased. V3" values showed significant correlation with the severity of clinical symptoms such as self-care, facies, posture, gait, speech, and Hoehn-Yahr's stage. On the other hand, V3" values were not significantly correlated with the degree of tremor, seborrhea, and duration of the illness. In conclusion, we found that SPECT of the [123I] beta-CIT is a useful method for the diagnosis in the patients presenting parkinsonism, and for the clinico-physiological estimation of parkinsonian symptoms such as self-care, facies, posture, gait, and speech.     

Dopamine transporter imaging (123)I-FP-CIT (DaTSCAN) SPET in differential diagnosis of dopa-responsive dystonia and young-onset Parkinson's disease

Dopa-responsive dystonia (DRD) is a genetic disorder characterized by childhood onset dystonia, dominant inheritance, diurnal symptoms fluctuation and positive levodopa response. Adult-onset DRD is frequently combined with parkinsonism and can be mistaken with young onset Parkinson's disease (YOPD). Both conditions are caused by dopamine deficiency, due to nigral cells' loss in YOPD, and due to enzymatic defects in dopamine synthesis in DRD. Single photon emission tomography (SPET) with (123)I-N--fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ((123)I-FP-CIT)-DaTSCAN is a sensitive neuroimaging method for the assessment of nigrostriatal dopaminergic system integrity and degeneration. Our aim was to evaluate the usefulness of (123)I-FP-CIT( DaTSCAN) SPET in the differential diagnosis of DRD and YOPD in clinical practice. Brain SPET with (123)I-FP-CIT was performed in 13 patients (7 males, 6 females), age 20-58 years, with mean age of onset of their disease, 29 years, eleven patients with early onset parkinsonian symptoms and 2 with genetically proved DRD. The images were evaluated by visual and semiquantitative analyses (ROI). The ratio of specific-striatal to non specific-occipital binding was calculated. Ten out of 11 patients with YOPD had decreased accumulation of DaTSCAN in striatum, especially in putamen, that is typical findings for Parkinson's disease. In three patients DaTSCAN was normal with symmetric tracer uptake in both striata, caudate nucleus and putamen and the diagnosis of DRD was suspected. Two patients with initial dystonic symptoms and genetically proved DRD had normal DaTSCAN. In one patient after normal DaTSCAN findings the initial diagnosis of YOPD was changed to the diagnosis of DRD. Region of interest (ROI) analyses have shown significantly lower(123)I-FP-CIT binding ratios in YOPD than in DRD in all 3 regions of interest: striatum (1.95±0.32) vs (2.76±0.10) P<0.001, putamen (1.76±0.25) vs (2.84±0.14) P<0.0001 and caudate nucleus (2.37±0.51) vs (3.27±0.14) P<0.01. In conclusion, our results indicate that DaTSCAN is an objective neuroimaging method able to distinguisch neurodegenerative disease YOPD from DRD and clarify a clinical dilemma, which is important for the treatment, prognosis and genetic counseling of patients and their families.     

Quantitative accuracy of dopaminergic neurotransmission imaging with (123)I SPECT.

123I-Labeled radiotracers are suitable for in vivo imaging of the dopaminergic system by SPECT. However, precise measurement of striatal uptake is limited by scatter, attenuation, and the finite spatial resolution of the camera. We studied the quantitative accuracy that can be achieved with (123)I SPECT of the dopaminergic neurotransmission system. METHODS: Using a Monte Carlo simulation and brain phantom experiments, we studied the biases in brain and striatal absolute uptake estimates and in binding potential (BP) values for different processing schemes with corrections for attenuation, scatter, and the partial-volume effect. RESULTS: Without any correction, brain activity was underestimated by at least 65%, and absolute striatal activity measured in regions corresponding to the anatomic contours of the striata was underestimated by about 90%. With scatter and attenuation corrections only, estimated brain activity was accurate within 10%; however, striatal activity remained underestimated by about 50%, and BP values were underestimated by more than 50%. When combined with attenuation and scatter corrections, anatomically guided partial-volume effect correction (PVC) reduced the biases in striatal activity estimates and in BP values to about 10%. PVC reliability was affected by errors in registering SPECT with anatomic images, in segmenting anatomic images, and in estimating the spatial resolution. With registration errors of 1 voxel (2.1 x 2.1 x 3.6 mm(3)) in all directions and of 15 degrees around the axial direction, PVC still improved the accuracy of striatal activity and BP estimates compared with scatter and attenuation corrections alone, the errors being within 25%. A 50% overestimation of the striatal volume yielded an approximate 30% change in striatal activity estimates with respect to no overestimation but still provided striatal activity estimates that were more accurate than those obtained without PVC (average errors +/- 1 SD were -22.5% +/- 1.0% with PVC and -49.0% +/- 5.5% without PVC). A 2-mm error in the spatial resolution estimate changed the striatal activity and BP estimates by no more than 10%. CONCLUSION: Accurate estimates of striatal uptake and BP in (123)I brain SPECT are feasible with PVC, even with small errors in registering SPECT with anatomic data or in segmenting the striata.     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.