Biomedical subjects

E A van Royen

Publications and source records attributed to E A van Royen.

At least 19 recordsLinked to original sources

PubMed2003

[(123)I]beta-CIT SPECT is a useful method for monitoring dopaminergic degeneration in early stage Parkinson's disease.

OBJECTIVES: To examine the validity of [(123)I]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 [(123)I]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 [(123)I]beta-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure. RESULTS: A decrease in [(123)I]beta-CIT binding ratios between the two images was found in all regions of interest. The average decrease in [(123)I]beta-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]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: [(123)I]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 [(123)I]beta-CIT binding to dopamine transporters. If the latter finding is replicated in larger groups of patients, it supports the suitability of [(123)I]beta-CIT SPECT for examining the progression of neurodegeneration in patients being treated with D(2)receptor agonists.

Antiparkinson Agents↗

PubMed2001

Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT.

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 [18F]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 [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]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 [123I]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 (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]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.

Adult↗

PubMed2001

Rigidity decreases resting tremor intensity in Parkinson's disease: A [(123)I]beta-CIT SPECT study in early, nonmedicated patients.

Tremor is one of the clinical hallmarks of Parkinson's disease (PD). Although it is accepted that other classic symptoms of PD such as rigidity and bradykinesia result from a degeneration of the nigrostriatal system and subsequent reduction in striatal dopamine, the pathophysiology of resting tremor remains unclear. The majority of recent single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies, using various radioligands, demonstrated significant correlation between striatal radioligand bindings and the degree of parkinsonian symptoms such as rigidity and bradykinesia, but not tremor. We investigate the relationship between the degeneration of the nigrostriatal pathway and the appearance of resting tremor, taking into account the possible interference of rigidity with the resting tremor. Thirty early and drug-naïve PD patients were examined. Tremor and rigidity of the arms were assessed using UPDRS, and the power of tremor was estimated using spectral analysis of tremor peaks. [(123)I]beta-CIT SPECT was used to assess degeneration of the dopaminergic system in PD patients. A comparison between asymmetry indices showed that in terms of both tremor and rigidity, the most affected arm corresponded significantly with the contralateral striatum, having the largest reduction in radioligand binding. Furthermore, tremor power accounted for a significant part of variance in the contralateral striatum, suggesting a relationship between this PD symptom and the degeneration of the dopaminergic system. Further, the degree of tremor was reduced with increasing rigidity. However, correcting for the influence of rigidity, the significant contribution of tremor in the variance in the contralateral striatal [(123)I]beta-CIT binding disappeared. When the confounding influence of rigidity is taken into account, no significant direct relationship between dopaminergic degeneration and the degree of tremor could be found. Other pathophysiological mechanisms should be similarly investigated in order to further our understanding of the origin of resting tremor in PD.

Adult↗

PubMed2001

Dopamine transporter density in patients with tardive dyskinesia: a single photon emission computed tomography study.

RATIONALE: Tardive dyskinesia occurs frequently in schizophrenic patients chronically treated with classical antipsychotic medication. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. OBJECTIVE: To evaluate dopamine transporter density in the striatum in patients with tardive dyskinesia. METHODS: Striatal [123I]FP-CIT binding was measured with SPECT in seven schizophrenic patients with tardive dyskinesia and eight healthy controls. RESULTS: No significant difference was found between striatal [123I]FP-CIT binding ratios in patients with tardive dyskinesia and controls. CONCLUSIONS: This preliminary study indicates no change in striatal dopamine transporter density in schizophrenic patients with tardive dyskinesia. This finding does not support the hypothesis that tardive dyskinesia is caused by dopaminergic cell loss.

Adult↗

PubMed2001

Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study.

RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine.

Adolescent↗

PubMed2001

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease.

We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43-73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Adult↗

PubMed2001

Quantitative analysis of 99Tcm-sestamibi myocardial perfusion SPECT using a three-dimensional reference heart: a comparison with experienced observers.

BACKGROUND: Quantification of myocardial perfusion single photon emission computed tomography (SPECT) may improve scintigraphic analysis. Recently, a fully operator independent technique for the quantification of myocardial perfusion SPECT was described, based on a normal three-dimensional averaged reference heart. The purpose of this study was to compare the automated SPECT quantification technique with experienced observers. METHODS: A total of 43 patients, 36 with one-vessel coronary artery disease (CAD) and seven with a low likelihood of CAD, underwent 99Tcm-sestamibi SPECT (99Tcm-MIBI SPECT). Three experienced observers and a panel (composed of the three observers), blinded to the clinical and angiographic data, analysed the size and severity of perfusion defects and the relation to the distribution areas of the coronary arteries. Inter-observer agreement was calculated by using kappa (kappa) statistics. RESULTS: The inter-observer agreement between the human observers and the automated quantitative analysis, for severity and size of perfusion abnormality, was moderate (kappa range 0.38-0.68), while this was fair between three individual observers (kappa range 0.36-0.87) and good between the individual observers and the panel (kappa range 0.63-0.89). There were no differences between the quantitative analysis and the panel in the allocation of perfusion abnormalities to the affected coronary artery. CONCLUSIONS: The operator independent quantification method showed a moderate agreement with individual observers and a panel analysis for size and severity of perfusion abnormalities. The automatic quantification has a similar ability to assign perfusion abnormalities to the diseased coronary artery as compared to an expert panel.

Adolescent↗

PubMed2000

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

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 [123I]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 [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]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.

Adult↗

PubMed2000

Evaluation of the long-term functional outcome assessed by myocardial perfusion scintigraphy following excimer laser angioplasty compared to balloon angioplasty in longer coronary lesions.

OBJECTIVES: Evaluation of the long-term functional outcome assessed by exercise myocardial perfusion imaging following excimer laser angioplasty compared to balloon angioplasty in coronary lesions > 10 mm in length. BACKGROUND: Previous randomized studies evaluating the effect of coronary interventions mainly focused on the long-term clinical and angiographic outcome. The functional outcome, assessed by myocardial perfusion scintigraphy, has not been evaluated in a randomized setting. METHODS: A total of 308 patients with stable angina and a longer coronary lesion (> 10 mm) were randomized to excimer laser angioplasty or balloon angioplasty. A 99mTechnetium-2-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) study was performed in 139 patients before the initial angioplasty procedure and at 6 months follow-up (73 patients in the laser group versus 66 patients in the balloon group, respectively). Exercise tolerance at follow-up was compared to baseline values by means of exercise duration and double product at peak exercise. Myocardial perfusion of the randomized vascular bed was assessed semi-quantitatively on the MIBI SPECT images. The reversible defects were graded as mild, moderate or severe. Myocardial perfusion at follow-up was expressed as a percentage reduction in incidence and grading of the reversible defects compared to baseline values. RESULTS: Forty-four (61%) patients assigned to laser angioplasty were asymptomatic at 6 months follow-up compared to 34 (52%) patients assigned to balloon angioplasty (p = NS). Improvement in exercise duration and double product were 0.7 +/- 2.1 min and 4.3 +/- 6.2 min/mmHg/l,000, respectively, in the laser group, versus 0.3 +/- 2.5 min and 3.1 +/- 5.5 min/mmHg/1,000, respectively, in the balloon group (both p = NS). The percentage reduction of reversible defects was 23% in patients assigned to laser angioplasty vs. 29% in patients assigned to balloon angioplasty (Relative risk [RR]: 0.79, 95% confidence interval [CI]: 0.40-1.57; p = 0.50). The mild, moderate and severe reversible defects improved in 44.4, 63.6 and 66.6%, respectively, in the laser angioplasty group vs. 66.6, 53.8 and 90%, respectively, in the balloon angioplasty group. None of the comparisons were significantly different. CONCLUSION: Excimer laser angioplasty compared to balloon angioplasty in coronary lesions > 10 mm in length yields a similar long-term functional outcome assessed by anginal status, exercise tolerance and myocardial perfusion.

Adult↗

PubMed1999

Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia.

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.

Adolescent↗

PubMed1999

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism.

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.

Carrier Proteins↗

PubMed1999

Octreotide-scintigraphy is a disease-activity parameter in Graves' ophthalmopathy.

OBJECTIVE: It is thought that immunosuppressive treatment of Graves' ophthalmopathy should be restricted to patients with active eye disease, but assessing disease activity is difficult. Octreotide scintigraphy has been claimed to differentiate active from inactive disease. Here we study the intraobserver variability and diagnostic accuracy of the quantitative measurement of orbital octreotide uptake. PATIENTS AND DESIGN: Twenty-two consecutive patients with moderately severe ophthalmopathy were treated with retrobulbar radiotherapy. Pretreatment octreotide scintigraphic data were related to the response at six months after radiotherapy, using Receiving-Operator-Characteristic curves. MEASUREMENTS: Octreotide uptake was measured at 4 and 24 h after i.v. injection of approximately 3 mCi (= 111 MBq; range 75-150 MBq) 111Indium-DTPA-Octreotide with a neuro-SPECT camera. Counts were measured in fixed regions-of-interest in 4 transversal slices of the orbit, the temporal and the occipital area. Measurements were done twice and intraobserver variability was analysed by coefficients of variations (CV). Uptake is expressed as orbital/background ratio. The nature of the temporal uptake was studied by matching an octreoscan with a technetium scan and MRI. RESULTS: Intra-observer variability of measuring octreotide uptake was acceptable, and the coefficient of variation slightly better using the orbital/occipital ratio (11%), than the orbital/temporal ratio (16%). From matching studies it appears that the temporal uptake takes place, in part, in the parotid gland. The orbital/occipital ratio was used to predict the outcome of radiotherapy. Mean (+/- SD) uptake on the 4 h scan was higher in responders (2.2 +/- 0.66) than in nonresponders (1.7 +/- 0.39; P = 0.04). From the Receiving-Operator-Characteristic curve we determined a cut-off value of 1.85, which yielded a positive predictive value of 92% and a negative predictive value of 70%. The 24 h scan could not predict a response. CONCLUSION: Quantitative measurement of orbital octreotide uptake is possible. Using the orbital/occipital ratio on the 4 h scan, the octreoscan seems useful in predicting response to subsequent radiotherapy. The 24 h scan seems not to be useful in predicting therapeutic outcome.

Adult↗

PubMed1999

Efficacy of monoclonal antibody 131I-B72.3 immunoscintigraphy of pancreatic adenocarcinoma xenografts in nude mice.

OBJECTIVE: To assess the efficacy of monoclonal antibody (MoAb) B72.3 for in vivo-immunoscintigraphy of pancreatic carcinoma in nude mice. DESIGN: Experimental controlled animal study. SETTING: University hospital, The Netherlands. SUBJECTS: 11 nude mice with subcutaneously xenografted human pancreatic carcinoma. INTERVENTIONS: Specific MoAb B72.3 and non-specific MoAb MOPC21 were iodinated with 131I and injected intraperitoneally in nude mice. Scintigrams were taken on days 1-10 and tumour:non-tumour ratios of the regions of interest (tumour, thorax, abdomen, background) were calculated. The mice were then killed for in vitro tissue counts. MAIN OUTCOME MEASURES: Tumour:non-tumour ratios in vivo and in vitro. RESULTS: Results of immunoscintigraphy on days 1, 2, and 6 were compared. In the B72.3-group all ratios were only moderately raised, the tumour:background ratio being the highest (2.35 (SD 0.67)) on day 6. There were no obvious differences between the ratios of the B72.3-group and the MOPC21-group. The results of tissue counts done at the end of the study, showed that tumour:non-tumour ratios were twice as high in the B72.3-group, suggesting some specificity of this MoAb. CONCLUSION: The results of our study suggest that MoAb B72.3 is not powerful enough for in vivo detection of pancreatic cancer as assessed in this xenograft model in nude mice.

Adenocarcinoma↗

PubMed1999

Functional assessment of coronary artery stenosis by doppler derived absolute and relative coronary blood flow velocity reserve in comparison with (99m)Tc MIBI SPECT.

OBJECTIVE: To determine the relation between the relative and absolute coronary blood flow velocity reserve (CFVR) compared with the results of (99m)Tc MIBI single photon emission computed tomography (SPECT). METHODS: In 37 patients with one vessel disease, (99m)Tc 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 1.9) and rCFVR (cut off value 0.65) with (99m)Tc 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 (99m)Tc 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.

Adult↗

PubMed1999

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

UNLABELLED: 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.

Brain↗

PubMed1999

Quantification and visualization of defects of the functional dopaminergic system using an automatic algorithm.

UNLABELLED: In SPECT, the binding of radiotracers in brain areas is usually assessed by manual positioning of regions of interest (ROIs). The disadvantages of this method are that it is an observer-dependent procedure and that it may not be sensitive for assessing defects significantly smaller than the ROI. To circumvent these limitations, we developed a fully automatic three-dimensional technique that quantifies neuronal radiotracer binding on a voxel-by-voxel basis. METHODS: To build a model of normal 123I-labeled N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane (FPCIT) binding, 17 studies of healthy volunteers were registered to the same orientation. After registration, the specific-to-nonspecific binding ratio was calculated for each voxel of the striatal volumes of interest (VOIs). The mean and SD of that binding ratio were then calculated on a voxel-by-voxel basis. For the analysis of 10 healthy volunteer studies (control group) and 21 studies of drug-naive patients with Parkinson's disease, the registration and calculation of the specific-to-nonspecific [123I]FPCIT binding ratio were performed by the same method. Subsequently, a voxel of the striata was classified as a diminished [123I]FPCIT binding ratio if its value was lower than the mean -2 x SD. For each subject, the defect size, the relative number of voxels with a diminished binding ratio and the binding ratio of the whole striatal VOIs were calculated and compared with the binding ratio as assessed by the traditional ROI method. RESULTS: The results of the automatic method correlated significantly with the results of the traditional ROI method. Furthermore, for the ipsilateral side, the automatically calculated defect size had less overlap between the patient and the control group than the traditionally calculated binding ratio. CONCLUSION: The method presented quantifies [123I]FPCIT binding ratio automatically on a voxel-by-voxel basis, by comparison with a model of healthy volunteers. We have shown that it is appropriate to use the automatic method as a replacement for the traditional manual method, which enables us to study the localized dopaminergic degeneration process in Parkinson's disease more precisely and without any inter- or intraobserver variability.

Algorithms↗

PubMed1998

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging.

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138-193 MBq Z-[123I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[123I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[123I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%+/-14% (SD) and that in faeces 31%+/-19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[123I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[123I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient.

Adult↗

PubMed1998

Iodine-123 labelled nor-beta-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats.

Iodine-123 labelled 2beta-carbomethoxy-3beta-4-iodophenylnortropane (nor-beta-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [123I]nor-beta-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [123I]nor-beta-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [123I]nor-beta-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [123I]nor-beta-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans.

Animals↗