123 I)β-CIT binding; and to determine the sample size and frequency of SPECT imaging required to demonstrate a significant effect of a putative neuroprotective agent. Methods: A group of 50 early stage Parkinson's disease patients was examined. Two SPECT imaging series were obtained, 12 months apart. The mean annual change in the ratio of specific to non-specific ( 123 I)β-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure. Results: A decrease in ( 123 I)β-CIT binding ratios between the two images was found in all regions of interest. The average decrease in ( 123 I)β-CIT binding ratios was about 8% in the whole striatum, 8% in the putaminal region, and 4% in the caudate region. Comparison of scans done in nine patients under two different conditions—in the off state and while on drug treatment—showed no significant alterations in the expression of striatal dopamine transporters as measured using ( 123 I)β-CIT SPECT. Power analysis indicated that to detect a significant (p < 0.05) effect of a neuroprotective agent with 0.80 power and 30% of predicted protection within two years, 216 patients are required in each group when the effects are measured in the whole putamen. Conclusions: (

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]β-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]β-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand,N-ω-fluoropropyl-2β-carbomethoxy-3β-(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]β-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]β-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]β-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

Objectives: To examine the validity of [I-123]beta-CIT SPECT for monitoring the progression of dopaminergic degeneration in Parkinson's disease; to investigate the influence of short term treatment with D-2 receptor agonists on striatal [I-123]beta-CIT binding; and to determine the sample size and frequency of SPECT imaging required to demonstrate a significant effect of a putative neuroprotective agent.Methods: A group of 50 early stage Parkinson's disease patients was examined. Two SPECT imaging series were obtained, 12 months apart. The mean annual change in the ratio of specific to non-specific [I-123]beta-CIT binding to the striaturn, putamen, and caudate nucleus was used as the outcome measure.Results: A decrease in [I-123]beta-CIT binding ratios between the two images was found in all regions of interest. The average decrease in [I-123]beta-CIT binding ratios was about 8% in the whole striaturn, 8% in the putaminal region, and 4% in the caudate region. Comparison of scans done in nine patients under two different conditions-in the off state and while on drug treatment-showed no significant alterations in the expression of striatal dopamine transporters as measured using [I-123]beta-CIT SPECT. Power analysis indicated that to detect a significant (p < 0.05) effect of a neuroprotective agent with 0.80 power and 30% of predicted protection within two years, 216 patients are required in each group when the effects are measured in the whole putamen.Conclusions: [I-123]beta-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in Parkinson's disease and may provide an objective method of measuring the effectiveness of neuroprotective treatments. Short term treatment with a D-2 agonist does not have a significant influence on [I-123]beta-CIT binding to dopamine transporters. If the latter finding is replicated in larger groups of patients, it supports the suitability of [I-123]beta-CIT SPECT for examining the progression of neurodegeneration in patients being treated with D-2 receptor agonists.

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Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [F-18]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [I-123]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied.Using [I-123]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia, Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine. eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included.Striatal [I-123]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76). patients treated with risperidone (2.76). AP-free patients (7.68) and controls (2.82) (F=0.07. p=0.98). Unexpectedly, striatal [I-123]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t = -2.56, p = 0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover. DA transporter density does not seem to be altered by AP medication. (C) 2001 Elsevier Science B.V. All rights reserved.

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer’s disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [I-123]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of +/-110 MBq [I-123]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [I-123]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [I-123]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [I-123]FP-CIT binding in young adults. Finally, females were found to have significantly higher [I-123]FP-CIT binding ratios than males. This effect of gender on [I-123]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

We determined the relationship between regional cerebral blood flow (rCBF) measured with single-photon emission tomography (SPET) and decline in cognitive function and survival in Alzheimer's disease. In a prospective follow-up study, 69 consecutively referred patients with early probable Alzheimer's disease (NINCDS/ADRDA criteria) underwent SPET performed at the time of initial diagnosis using technetium-99m-labelled hexamethylpropylene amine oxime. Neuropsychological function was assessed at baseline and after 6 months and survival data were available on all patients, extending to 5.5 years of follow-up. Lower left temporal (P<0.01) and lower left parietal (P<0.01) rCBF were statistically significantly related to decline in language function after 6 months. The association between left temporal rCBF and survival was also statistically significant (P<0.05) using Cox proportional hazards regression analysis. Performing analysis with quartiles of the distribution, we found a threshold effect for low left temporal rCBF (rCBF<73.7%, P<0. 01) and high risk of mortality. In this lowest quartile, median survival time was 2.7 years (follow-up to 5.2 years), compared with 4.4 years in the other quartiles (follow-up to 5.5 years). Kaplan-Meier survival curves showed statistically significant (P<0. 05, log rank test) survival curves for the lowest versus other quartiles of left temporal rCBF. All results were unaffected by adjustment for age, sex, dementia severity, duration of symptoms, education and ratings of local cortical atrophy. We conclude that left temporal rCBF predicts decline in language function and survival in patients with early probable Alzheimer's disease, with a threshold effect of low rCBF and high risk of mortality.

Parkinson's disease is characterized by degeneration of dopaminergic neurons, resulting in loss of dopamine transporters in the striatum. Recently, the tracer I-123-N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (FPCIT) was developed for imaging dopamine transporters with SPECT. The purpose of this study was to develop an [I-123]FPCIT SPECT protocol for routine clinical studies. Methods: We examined the time course of [I-123]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 [I-123]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 [I-123]FPCIT binding was stable in both groups, although, as expected, it was significantly lower in patients. In the patients, [I-123]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 [I-123]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 [I-123]FPCIT SPECT technique is sensitive enough to distinguish control subjects from patients with Parkinson's disease, even at an early stage of the disease.

A crucial characteristic of antipsychotic medication is the occupancy of the dopamine (DA) D2 receptor. We assessed striatal DA D2 receptor occupancy by olanzapine and risperidone in 36 young patients [31 males, 5 females; mean age 21.1 years (16–28)] with first episode schizophrenia, using [123I]iodobenzamide (IBZM) SPECT. The occupancy of DA D2 receptors was not significantly different between olanzapine and risperidone. However, in subgroups of most prescribed doses, DA D2 occupancy was higher in the risperidone 4-mg group (79%) compared to the olanzapine 15-mg group (62%). [123I]IBZM binding ratios decreased with olanzapine dose (r=−0.551; P<0.01), indicating higher DA D2 receptor occupancy with higher olanzapine dose. Akathisia and positive symptoms were correlated with [123I]IBZM binding ratio (r=−0.442; P<0.01; and r=−0.360; P<0.05, respectively). Prolactin (PRL) levels were elevated in the risperidone, but not in the olanzapine group, at comparable D2 receptor occupancy levels. In the olanzapine group, PRL levels were correlated with [123I]IBZM binding ratio (r=−0.551; P<0.01). In conclusion, both olanzapine and risperidone induce a high striatal D2 receptor occupancy, dependent on dose and group formation. The lower incidence of prolactin elevation with olanzapine, compared to risperidone, may not be attributed to a lower D2 receptor occupancy.

Objective-To determine the relation between the relative and absolute coronary blood flow velocity reserve (CFVR) compared with the results of Tc-99m MIBI single photon emission computed tomography (SPECT).Methods-In 37 patients with one vessel disease, Tc-99m MIBI SPECT was performed before angioplasty, two to three weeks after angioplasty, and at six months' follow up. CFVR was measured distal to the stenosis (dCFVR) as well as in a reference coronary artery before angioplasty, immediately after angioplasty, and at late follow up. Relative CFVR (rCFVR) was calculated as the ratio between dCFVR and CFVR measured in the reference coronary artery. The optimal thresholds for reversible perfusion defects were calculated using receiver operating characteristic curves.Results-The agreement for the full range of coronary artery stenosis (n = 107, mean (SD) diameter stenosis 48 (28)%, range 0-98%) between dCFVR (cut off value 1.3) and rCFVR (cut off value 0.65) with Tc-99m MIBI SPECT was 81% and 85%, respectively. In intermediate lesions (n = 49, diameter stenosis range 30-75%) the agreement between dCFVR (cut off value 2.0) and Tc-99m MIBI SPECT was 72%, which increased to 78% using the rCFVR (cut off value 0.65). There was a strong linear relation between dCFVR and rCFVR (r = 0.93, p < 0.0001).Conclusions A best cut off value for dCFVR of 1.9 corresponds with a best cut off value of 0.65 for rCFVR, within the full range of coronary narrowings. Intracoronary blood flow velocity analysis could obviate the need for additional myocardial perfusion scintigraphy in the majority of patients.

BACKGROUND:Nicotinamide (NAM) and carbogen both have been shown to enhance the radiation effect in rodent tumour models and are currently being tested in clinical trials. These agents have demonstrated to act against hypoxia and one of their underlying mechanisms could be an increase of tumour blood perfusion.PURPOSE:To analyse the effect of both agents on normal brain perfusion and tumour perfusion in patients with glioblastoma.MATERIALS AND METHODS:Nineteen patients with glioblastoma were studied with 99mtechnetium-hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc-HMPAO SPECT) before and after administration of carbogen and/or NAM. Another six patients were studied with the same procedure but without any flow modulator and were used as controls.RESULTS:Although the variations between patients were large, no significant enhancement in mean tumour and normal brain perfusion could be demonstrated with NAM or carbogen compared to the control patients. Also no consistent changes in the mean perfusion ratio between tumour and surrounding normal brain were found, suggesting an absence of a selective perfusion effect.CONCLUSIONS:No significant influence of carbogen and/or NAM on tumour perfusion and normal brain perfusion could be detected with SPECT in patients with glioblastoma.

UNLABELLED:The aims of this study were to investigate whether the loss of striatal dopamine transporters in early and drug-naive patients with Parkinson's disease could be demonstrated by means of 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)tropane (123I-FP-CIT) SPECT in a 1-day protocol and whether the SPECT measures were correlated with disease severity.METHODS:Twenty-one early-stage and drug-naive Parkinson's disease patients (age range 42-73 yr; mean age 55.5 yr) and 14 healthy controls (age range 28-83 yr; mean age 53.6 yr) were examined. SPECT image acquisition was always performed at 3 hr postinjection. The ratio of specific to nonspecific striatal 123I-FP-CIT binding was used as the outcome measure.RESULTS:All striatal 123I-FP-CIT ratios were significantly lower in the Parkinson's disease group compared to those in the control group. The mean reduction in the putamen was 57% of the control mean, and that in the caudate nucleus was 29% of the control mean. Patients with unilateral Parkinson's disease showed a bilateral loss of striatal 123I-FP-CIT binding. Discriminant function analysis, using the 123I-FP-CIT SPECT data of the ipsilateral and contralateral putamen, predicted group membership in all cases; the contralateral putamen accounted for the greatest difference between the Parkinson's disease patients and the controls. In the control group, a clear decline in 123I-FP-CIT binding was found with aging, amounting to 9.6%/decade. Unexpectedly, in the Parkinson's disease group, regression analysis revealed that neither severity of disease nor age accounted for a significant part of the variance in striatal SPECT measures.CONCLUSION:Our findings indicate that 123I-FP-CIT SPECT is a reliable method to discriminate between early, drug-naive Parkinson's disease patients and healthy controls and to identify patients in the preclinical phase of Parkinson's disease. Possibly due to the relatively homogeneous group of Parkinson's disease patients and the use of a suboptimal outcome measure, no significant correlations were found between striatal 123I-FP-CIT binding ratios and disease severity, such as were established earlier with 123I-beta-CIT. Further research is necessary to interpret these findings.

UNLABELLED:Several SPECT studies reported decreased striatal 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane ([123I]FP-CIT) binding in patients with Parkinson's disease. For application in routine clinical studies, information on the reliability and reproducibility of the [123I]FP-CIT SPECT technique is critical. This study reports on the reliability and reproducibility of [I23I]FP-CIT SPECT in healthy control subjects and patients with Parkinson's disease using two different analysis protocols: the conventional region of interest (ROI) protocol and a newly developed, fully automatic, operator-independent volume of interest (VOI) protocol.METHODS:We performed repeated [123I]FP-CIT SPECT scans in 6 healthy control subjects and 10 patients with Parkinson's disease to measure scan-to-scan variations. Scintigraphic data were analyzed 3 hr after injection of the radiotracer.RESULTS:In controls, the mean test/retest for the ratio of the striatal-to-nonspecific [123I]FP-CIT uptake were (3.79 +/- 0.67/3.82 +/- 0.74) and (4.16 +/- 0.70/4.08 +/- 0.97) for the ROI and VOI technique, respectively. No significant differences were measured between test/retest studies. The mean test/retest variability for the ROI technique was low (7.25%) with excellent reliability (rho = 0.99). In addition, the mean test/retest variability for the VOI technique was also low (7.47%) with very high reliability (rho = 0.95). In Parkinson's disease patients, we found mean test/retest for the striatal-to-nonspecific [123I]FP-CIT ratio of (1.78 +/- 0.23/1.79 +/- 0.25) and (1.83 +/- 0.31/1.85 +/- 0.35) using the ROI and VOI technique, respectively. Also in patients, these results did not differ significantly between test/retest studies. The mean test/retest variability for the ROI technique was low (7.90%) with excellent reliability (rho = 1.00). In addition, the mean test/retest variability for the VOI technique was also low (7.36%) with high reliability (rho = 0.96).CONCLUSION:Reliable and reproducible results were obtained with the ROI, as well as the VOI technique, for the analysis of striatal dopamine transporters with [123I]FP-CIT SPECT in healthy controls and Parkinson's disease patients. The use of an operator-independent method will be a great advantage in routine clinical studies.