[123I]Iodoamphetamine SPECT imaging

SPECT imaging of [¹²³I]IMP is reviewed. Methods for radiopharmaceutical production are discussed with an emphasis on labeling small quantities of IMP. Limited angle tomography and full angle SPECT with standard cameras and special imaging systems are reviewed. Selection of collimator and methods of reconstruction are discussed. Clinical studies are described with emphasis on stroke, epilepsy and dementia. The efforts to perform quantitative imaging of rCBF with [¹²³I]IMP are reviewed.     

Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [123I]ss-CIT and high-resolution SPET.

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriatal dopaminergic function in WD in relation to different courses and severity of the disease. Using high-resolution single-photon emission tomography (SPET) after administration of 2ss-carbomethoxy-3ss-(4[123I]iodophenyl)tropane ([123I]ss-CIT), striatal dopamine transporters (DAT) were imaged in 43 WD patients and a control group of ten subjects. From the SPET images, specific [123I]ss-CIT binding ratios were obtained for the caudate heads, putamina and entire corpus striatum. In addition, to evaluate a putative dissociation between the caudate and putaminal [123I]ss-CIT binding ratios, the ratio between these binding ratios was calculated (CA/PU ratio). The SPET data were compared with clinical data on the course of the disease (CD), the severity of neurological symptoms and the degree of hepatic alteration. Whereas the specific regional [123I]ss-CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the control group (e.g. striatal ratios: 13.4+/-3.0 vs 11.7+/-2.8), in patients with neurological CD the ratios were significantly reduced for all striatal substructures (P=0.003 after one-factor ANOVA). For the different subgroups a tendency was detected towards a stepwise decrease in the specific [123I]ss-CIT binding ratios from pseudo-sclerosis CD (9.4+/-2.3), through pseudo-parkinsonian CD (9.1+/-2.1) to arrhythmic-hyperkinetic CD (8.5+/-1.6). However, these group differences reached significance only for the comparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was significantly higher in WD than in the control group (1.30+/-0.19 vs 1.11+/-0.08; P=0.003). Severity of neurological symptoms was significantly correlated with all specific regional [123I]ss-CIT binding ratios (r=-0.49 to -0.57). For degree of liver alteration, significant correlations were obtained with the putaminal binding ratio (r=-0.37) and the CA/PU ratio (r=0.44). From these results is concluded that in WD the nigrostriatal dopaminergic function is compromised to varying extents. The degree of this presynaptic alteration of dopaminergic neurotransmission depends on the clinical course and severity of this copper deposition brain disorder and also varies in the different striatal substructures.     

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.     

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.     

Validation of brain tumour imaging with p-[123I]iodo-l-phenylalanine and SPECT

Purpose The aims of this prospective study were to validate single-photon emission computed tomography (SPECT) with p-[¹²³I]iodo-l-phenylalanine (IPA) in brain tumours and to evaluate its potential for the characterisation of indeterminate brain lesions.Methods In 45 patients with indeterminate brain lesions or suspected progression of glioma, amino acid uptake was studied using IPA-SPECT and compared with the final diagnosis established by biopsy or serial imaging. After image fusion of IPA-SPECT and magnetic resonance imaging, the presence of tumour was visually determined by two independent observers. IPA uptake was quantified as the ratio between maximum uptake in the suspicious lesion and mean uptake in unaffected brain.Results Primary brain tumours were present in 35 cases (12 low-grade and 23 high-grade gliomas). Non-neoplastic brain lesions were confirmed in seven cases (three dysplasias, three inflammatory lesions, one lesion after effective therapy). Visual analysis showed a high concordance between the two observers (kappa=0.90, p<0.001), with sensitivity and specificity of 86% and 100% for the discrimination of primary brain tumours and non-neoplastic lesions. At 30 min p.i., IPA uptake in primary brain tumours was higher than that in non-neoplastic lesions (1.70±0.36 vs 1.14±0.18, p<0.05). Brain metastases showed no increased uptake (1.13±0.22, n=3). The persistent retention of IPA in low-grade gliomas without disruption of the blood–brain barrier was visualised up to 24 h p.i. Low-grade and high-grade gliomas showed equivalent IPA uptake (1.72±0.37 vs 1.67±0.36 at 30 min, p=0.745).Conclusion IPA shows long and specific retention in gliomas. IPA is a promising and safe radiopharmaceutical for the visualisation of gliomas and the characterisation of indeterminate brain lesions.     

Initial experience with SPECT examinations using [123I]IBZM as a D2-dopamine receptor antagonist in Parkinson's disease.

[123I]IBZM is a new radioactive labelled ligand which has a high affinity and specificity to D2-dopamine receptors. The in vivo kinetics of [123I]IBZM were studied in patients with unilateral and bilateral accentuated idiopathic Parkinson's disease. The uptake in the basal ganglias and the imaging properties of this D2 receptor antagonist as a radiopharmaceutical for SPECT examinations had to be investigated. 5 patients, aged 42-66 years, (2 m/3 f) were examined. Each patient received 185 MBq [123I]IBZM intravenously. Blood samples were taken 0-120 min post injection (p.i.) and time activity curves were plotted. Three SPECT examinations were performed (I: 30-50 min; II: 50-70 min; and III: 70-90 min p.i.). The count rates (counts/pixel) in the basal ganglias and the cerebellum were measured for each SPECT series on transverse slices using the region-of-interest technique. The time-activity curve of [123I]IBZM shows a rapid decline in plasma during the first 10 min followed by a plateau until 120 min after injection. The SPECT examinations demonstrate the highest count rate in the basal ganglia during SPECT series III (i.e., 70-90 min p.i.). The side-to-side difference of the count rates were in the range of 3% in four patients, and 10% in one patient. The biokinetic data of [123I]IBZM make this substance capable as a radiopharmaceutical for SPECT examinations. The basal ganglia are best visualized 70-90 min p.i., thus [123I]IBZM seems to be a promising imaging agent for diseases of the D2-dopaminergic receptor system.     

Clinical impact of correlative [123I]-FP-CIT brain imaging and neurological findings in suspect Parkinson's disease

PURPOSE: Here we report our experience in a general hospital setting using [(123)I]-FP-CIT SPECT to diagnose patients with suspect Parkinson's disease (PD). MATERIALS AND METHODS: Thirty consecutive patients (19M, 11W, mean age: 61+/-13 years) were prospectively studied. Patients underwent MRI (27) at 1.5T or CT (3) when MRI was contraindicated, to rule out focal brain abnormalities. Motor and cognitive function were evaluated by neurologists with UPDRS and Hoehn e Yahr Scale. [(123)I]-FP-CIT striatal uptake, assessed with SPECT, was classified as normal, non-diagnostic, abnormal (unilateral or bilateral). Imaging results (SPECT+MRI) were correlated with the neurological findings. RESULTS: In 5 patients the [(123)I]-FP-CIT brain SPECT was normal, suggesting that their symptoms could be related to a benign disorder such as essential tremor. Two patients had non-diagnostic [(123)I]-FP-CIT brain SPECT, with MRI/CT findings compatible with subcortical cerebrovascular disease. In the remaining 23 patients abnormal striatal [(123)I]-FP-CIT uptake correlated with neurological findings, significantly increasing the probability of Parkinson's disease. In these patients MRI/CT scans were normal, or showed a mild BA, or mild cerebral vascular disease (mild CVD). CONCLUSIONS: Our results suggest that [(123)I]-FP-CIT scan could be used routinely in clinical practice to support the diagnosis of PD and to differentiate between other conditions. Moreover, FP-CIT could significantly impact treatment selection and follow-up of these patients.     

Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

Background [¹²³I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([¹²³I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Discussion Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [¹²³I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient’s care and taking into account the pros and cons of doing so.     

SPECT imaging with the serotonin transporter radiotracer [123I]p ZIENT in nonhuman primate brain

IntroductionSerotonin dysfunction has been linked to a variety of psychiatric diseases; however, an adequate SPECT radioligand to probe the serotonin transporter system has not been successfully developed. The purpose of this study was to characterize and determine the in vivo selectivity of iodine-123-labeled 2β-carbomethoxy-3β-(4′-((Z)-2-iodoethenyl)phenyl)nortropane, [¹²³I]p ZIENT, in nonhuman primate brain.MethodsTwo ovariohysterectomized female baboons participated in nine studies (one bolus and eight bolus to constant infusion at a ratio of 9.0 h) to evaluate [¹²³I]p ZIENT. To evaluate the selectivity of [¹²³I]p ZIENT, the serotonin transporter blockers fenfluramine (1.5, 2.5 mg/kg) and citalopram (5 mg/kg), the dopamine transporter blocker methylphenidate (0.5 mg/kg) and the norepinephrine transporter blocker nisoxetine (1 mg/kg) were given at 8 h post-radiotracer injection.ResultsIn the bolus to constant infusion studies, equilibrium was established by 4–8 h. [¹²³I]p ZIENT was 93% and 90% protein bound in the two baboons and there was no detection of lipophilic radiolabeled metabolites entering the brain. In the high-density serotonin transporter regions (diencephalon and brainstem), fenfluramine and citalopram resulted in 35–71% and 129–151% displacement, respectively, whereas methylphenidate and nisoxetine did not produce significant changes (<10%).ConclusionThese findings suggest that [¹²³I]p ZIENT is a favorable compound for in vivo SPECT imaging of serotonin transporters with negligible binding to norepinephrine and dopamine transporters.     

Test-retest reproducibility of extrastriatal dopamine D2 receptor imaging with [123I]epidepride SPECT in humans.

This study evaluated the test-retest reproducibility of D2 receptor quantification in the thalamus and temporal cortex using [123I]epidepride SPECT. METHODS: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) underwent 2 SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusion paradigm (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma clearance (in liters per hour) and free fraction (f1) of the parent tracer were measured. Radioactivity (in becquerels per gram) in the thalamus, temporal cortex, and cerebellum were normalized to the infusion rate (in becquerels per hour). Normalized striatal radioactivity was also measured to assess reproducibility in regions with a high density of receptors and better counting statistics. The outcome measures obtained were V3 (receptor density [Bmax]/equilibrium dissociation constant [KD]), V3' (f1 x Bmax/KD), and RT (specific-to-nondisplaceable tissue ratio). RESULTS: Test-retest variability and reliability (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for plasma clearance and 15.3% and 0.77, respectively, for f1. The test-retest variability of brain-specific (target minus nondisplaceable) radioactivity was higher in the thalamus and temporal cortex than in the striatum, although reliability was comparable. Among the outcome measures, V3' showed better test-retest variability and reliability in the thalamus (13.3% and 0.75, respectively) and temporal cortex (13.4% and 0.86, respectively). CONCLUSION: Brain radioactivity was the main source of variability for quantification of extrastriatal D2 receptors with [123I]epidepride. The reproducibility of outcome measures in extrastriatal regions was good. However, because receptor density was lower in extrastriatal regions than in the striatum, the counting statistics in these regions were low and reproducibility was affected by the higher test-retest variability of brain-specific radioactivity. Compared with V3 and V3', RT showed less test-retest variability in the thalamus and temporal cortex but lower reliability. Moreover, measurement of RT may be affected by the presence of potential lipophilic metabolites entering the brain.     

123I-FP-CIT semi-quantitative SPECT detects preclinical bilateral dopaminergic deficit in early Parkinson's disease with unilateral symptoms

BACKGROUND AND AIM: 123I-FP-CIT SPECT has been successfully used to detect the loss of dopaminergic nigrostriatal neurons in Parkinson's disease at an early stage. In this study we evaluated the capacity of 123I-FP-CIT SPECT to assess bilateral dopamine transporter (DAT) loss in de-novo hemi-Parkinson's disease (PD) patients with one-sided clinical symptoms. PATIENTS AND METHODS: Twenty-nine de-novo hemi-PD patients at an early stage (Hoehn & Yahr stage 1) and 18 gender and age matched healthy subjects were studied. 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(put)/O), and the putamen to caudate nucleus index (P(put)/C) were calculated in both the basal ganglia. RESULTS: In PD patients S/O, C/O and P(put)/O ratio values contralateral to the clinically affected side were significantly lower (P<0.001) than in the control group (-38%, -34% and -42%, respectively). A significant reduction (P<0.001) of the striatal binding ratios was also found ipsilaterally (S/O, -31%; C/O, -28%; P(put)/O, -33%). The P(put)/C index was also bilaterally significantly reduced (P<0.01). DAT loss was significantly greater (P<0.001) in the contralateral than in the ipsilateral S; and putamen bilaterally presented a higher dopaminergic deficit than did caudate. CONCLUSION: Our results indicate that semi-quantitative 123I-FP-CIT SPECT detects a bilateral dopaminergic deficit in early PD with unilateral symptoms and preclinical DAT loss in the ipsilateral striatal binding, corresponding to the side not yet affected by motor signs. Semi-quantitative analysis may thus be used to diagnose PD at an early stage as well as to identify individuals developing bilateral dopaminergic damage.     

Radiosynthesis of high effective specific-activity [123I]SCH 23982 for dopamine D-1 receptor-based SPECT imaging

The high yield, high-specific activity radiosynthesis of the dopaminergic D-1 receptor-binding ligand [¹²³I]SCH 23982 is described. Using no-carrier-added iododeprotonation of the des-iodo precursor SKF 83692 and column-switching HPLC, [¹²³I]SCH 23982 was isolated in 35–40% radiochemical yield with an effective specific activity of 2250–4000 Ci/mmol and an overall preparation time of 90 min. The procedure outlined here can be employed for the clinical production of [¹²³I]SCH 23982 as a SPECT radiopharmaceutical, as well as [¹²⁵I]SCH 23982 to be used for in vitro receptor-binding applications.     

Comparison of 4 methods for quantification of dopamine transporters by SPECT with [123I]IACFT.

2Beta-carbomethoxy-3beta-(4-fluorophenyl)-n-(1-iodoprop-1-en -3-yl) nortropane (IACFT) is a highly selective ligand for dopamine transporter (DAT) sites in the striatum. Recent reports have described the basic kinetics, neurobiology, and imaging properties of [123I]IACFT. This report focuses on the structural (i.e., the ability to produce consistent binding estimates) validity of 4 methods to quantify striatal binding potential (BP) for IACFT. METHODS: Seven healthy volunteers and 8 patients with Parkinson's disease were subjects for this study. Dynamic SPECT images and arterial blood samples were acquired during the 1.5-2 h after injection of 185-370 MBq [123I]IACFT. Plasma radioactivity was analyzed chromatographically to obtain metabolite-corrected arterial input functions. The k3/k4 ratio (BP) for striatal DAT sites was calculated by 4 methods. In the first method, tissue time-activity curves and metabolite-corrected arterial input functions were analyzed by a linear graphic method developed for reversible receptor ligands. The second method was also graphic; however, the occipital cortex time-activity curve was used as the input function. In the third method, the difference between the striatal and occipital cortex time-activity curves at secular equilibrium was taken to represent bound tracer, the occipital cortex time-activity curve was used to represent tracer in the free and nonspecifically bound state, and equilibrium receptor equations were used to determine BP. The fourth method used the occipital cortex time-activity curve to mathematically derive an input function for fitting the striatal time-activity curve and to determine BP. RESULTS: Analysis of the dynamic SPECT data by methods 1 and 2 resulted in highly linear plots (after approximately 15 min), supporting the reversibility of the tracer. A high linear correlation was found for BP determined by all 4 methods. ANOVA showed that methods 1-3 were indistinguishable; method 4 yielded lower BPs than did methods 1-3. CONCLUSION: These results show that BP can be estimated consistently using 4 different methods. This finding lends support to the modeling assumptions and provides methods suitable for clinical investigation.     

N-isopropyl-p-[123I]iodoamphetamine SPECT in MELAS syndrome: comparison with CT and MR imaging

Regional cerebral perfusion was studied in three patients with the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, using single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine (IMP). Accumulation of the tracer was relatively decreased in the parietooccipital regions and also in the frontotemporal regions after stroke-like episodes. However, quantitative regional cerebral blood flow (rCBF) measurement showed that rCBF was relatively well preserved even at these sites, and a hyperemic state was observed at the sites of normal accumulation. IMP SPECT may be useful in the diagnosis and assessment of the progress of the MELAS syndrome.     

SPECT imaging with [123I]-beta-CIT in Parkinsonism: comparison of SPECT images obtained by a single-headed and a three-headed gamma camera

Single photon emission computed tomography (SPECT) imaging of dopamine transporters by using the cocaine derivative [123I]-(1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]-beta-CIT) has been shown to be useful in patients with Parkinsonism. The aim of this study was to compare beta-CIT imaging with single-headed (SHS) and three-headed gamma camera systems (THS). In 17 patients with Parkinsonism, SPECT imaging with an SHS and a THS was performed 24 h after injection of 180 MBq of [123I]-beta-CIT. The SPECT studies were evaluated by visual assessment of the caudate nucleus (CN) and the putamen (PT) and the calculation of the striatal/cerebellar (S/C) ratios (with additional comparison to clinical symptoms measured by the Unified Parkinson's Disease Rating Scale (UPDRS)). The S/C ratios measured by the SHS and THS showed highly significant correlation (two-tailed P < 0.01) with Spearman correlation coefficients (SCCs) of 0.864 for the right side, 0.676 for the left side, and 0.761 for both sides. By the SHS, a sufficient visual differentiation between the CN and the PT could not be achieved. A significantly better distinction could be achieved by using the THS (Wilcoxon P<0.05). The S/C ratios of the THS only showed a significant (P < 0.05) SCC of -0.514 comparing to the UPDRS. Pathological alterations in the beta-CIT uptake pattern could be identified by using the SHS, but a significantly better differentiation of CN and the PT was possible by using the THS. The significant correlation of the S/C ratios measured by THS only emphasizes the value of THS in beta-CIT imaging.     

Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease.

(E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with (123)I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed (123)I-PE2I SPECT on healthy volunteers and patients with Parkinson's disease (PD) to validate the Logan graphical method for quantification of (123)I-PE2I binding and to analyze the relationship between (123)I-PE2I SPECT and clinical features of this frequent degenerative disease. METHODS: Eight PD patients (3 women, 5 men; mean age, 64 +/- 7.9 y; disease duration range, 1-8 y, Hoehn and Yahr stage range, 1-2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 +/- 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 +/- 30 MBq of (123)I-PE2I. RESULTS: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. (123)I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, (123)I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, (123)I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that (123)I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. CONCLUSION: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that (123)I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that (123)I-PE2I SPECT can be used for preclinical and early diagnosis of PD.     

123I]IPCIT and [123I]beta-CIT as SPECT tracers for the dopamine transporter: a comparative analysis in nonhuman primates

[123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]-CIT) and its isopropylester analog [123I]PCIT, both of which are phenyltropane derivatives of cocaine with high affinity for the dopamine (DA) transporter, were compared using single photon emission computed tomography in nonhuman primates. Although IPCIT is significantly more selective for the DA transporter than beta-CIT, striatal distribution volumes of specifically bound tracer were similar for both tracers. Compartmental modeling results were compared with a simple peak equilibrium method used previously by this group. The peak equilibrium method is shown to overestimate striatal distribution volumes, primarily due to a difference in the calculated time of peak specific uptake.     

A case of Creutzfeldt-Jakob disease followed up by N-isopropyl-[123I]-p-iodoamphetamine and 99mTc-hexamethylpropyleneamine oxime SPECT

N-isopropyl-[123I]-p-iodoamphetamine (123I-IMP) and 99mTc-hexamethylpropyleneamine oxime (99mTc-HM-PAO) SPECT were performed in a 66 yrs-old female patient with Creutzfeldt-Jakob disease (CJD). The decreased accumulation of both radiopharmaceuticals, which localized initially in the focal regions and progressed eventually to the whole brain, were observed in the early stage of CJD, when no abnormal findings were obtained on X-CT. Although the redistribution of 123I-IMP was recognized in the relatively early stage in which the accumulation was significantly decreased, it disappeared with the progression of the disease. The accumulation of both radiopharmaceuticals which decreased remarkably in the early stage of CJD was sustained in low level during the chronic stage. The accumulation ratio of 99mTc-HM-PAO, after second examinations, to that on first SPECT was lower than those of 123I-IMP. It was suggested, as this cause, that the difference of the accumulation mechanism of both agents might be concerned. Thus, it is interested to follow up a patient with CJD by using 123I-IMP and 99mTc-HM-PAO SPECT, and this modality will provide a useful information to clarify the pathogenesis of CJD.