Dopaminergic neurotransmission in patients with schizophrenia in relation to positive and negative symptoms.

Schizophrenia is a complex dynamic disorder comprising a wide range of neurobiological alterations including dopaminergic dysfunction. The aim of the study was to investigate dynamic changes of dopaminergic neurotransmission in patients with schizophrenia (n=8, mean age 25.4 ± 5.8 years) in early stages of the disorder, compared to healthy control subjects (n=7, mean age 23.6 ± 2.7 years). A dynamic IBZM SPECT protocol was used to assess the endogenous dopamine release following an amphetamine challenge. Subjects received a bolus activity of 175 MBq followed by a continuous infusion of 45 MBq/h [123I]IBZM. SPECT scans were performed 2 h after bolus injection, and 1 h following the amphetamine challenge (0.3 mg/kg). Striatal IBZM binding to dopamine D2 receptors was assessed with a volume-of-interest (VOI) technique. The change in IBZM binding between pre- and post-challenge scans was used as a measure of endogenous dopamine release triggered by amphetamine. At baseline, patients showed higher mean striatal IBZM binding compared to controls (0.77 ± 0.09 vs. 0.68 ± 0.07, p=0.07). There was a statistically significant difference in IBZM binding between patients, with a predominance of negative vs. positive symptoms (0.84 ± 0.08 vs. 0.71 ± 0.04, p<0.05). Upon amphetamine challenge, mean IBZM binding decreased by about 4.9 ± 7.6% in controls (n=7) compared to a mean of 12.4 ± 5.8% in subjects with schizophrenia (p<0.05). In patients, paranoid symptoms showed a significant negative correlation with IBZM baseline binding, whereas there was a trend towards positive correlation with the decrease of IBZM binding under challenge. Negative symptoms showed positive associations with baseline IBZM binding. The data are in line with previous reports and contribute to the notion of a dynamic instability of the dopaminergic system in patients with schizophrenia, taking into account the psychopathology with respect to positive or negative symptoms.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

Correction to: Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients.

The published article has an error in the first name initial of one of the authors. "M. Justinger" should be "C. Justinger" as shown in this erratum.

Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients.

INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naïve patients after yttrium-90 (Y-90) radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median survival was 15 months. Survival was significantly (p = 0.009) prolonged in patients with tumor burden of ≤ 25% (n = 8, OS 37.5 months) versus those with a tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival in therapy-naïve patients with unresectable ICC treated with Y-90 RE therapy only.

Equipment-independent reference values for dopamine transporter imaging with 123I-FP-CIT.

AIM: Reliable reference values are helpful to interpret and compare the results of dopamine transporter imaging with SPECT. Since semi-quantitative reference values cannot be easily transferred between imaging equipments, this study aimed to establish equipment independent normal values for the true striatal binding of 123I-FP-CIT. PATIENTS, METHODS: Specific striatal FP-CIT binding of 6 healthy volunteers and 26 patients with essential tremor were used to generate a reference range by applying an equipment specific resolution dependent factor to compensate for recovery effects. This factor has been determined previously by a series of standardized phantom measurements of an anthropomorphic basal ganglia phantom. Herewith, the resulting DAT binding values represent the expected true specific binding in the striatum. RESULTS: On average, true specific striatal binding was 5.83 +/- 0.96 in healthy controls, 5.25 +/- 0.67 in patients with essential tremor and 5.36 +/- 0.75 in the entire study cohort. CONCLUSION: These preliminary results may serve as a basis for the generation of a generally accepted equipment independent reference range for dopamine transporter imaging with 123I-FP-CIT. By a simple phantom measurement that can be accomplished within one day factors related to specific imaging equipment and processing can be corrected for, resulting in specific binding values which may enable a more standardized interpretation of dopamine transporter scans.

Detection of hepatocellular carcinoma with a new alpha-fetoprotein antibody imaging kit.

PURPOSE: The aim of this phase II study was to assess the clinical utility and safety of AFP-Scan (Immunomedics, Inc, Morris Plains, NJ), a technetium-99m (99mTc)-labeled anti-alpha-fetoprotein (AFP) Fab' imaging kit, in the evaluation of hepatocellular carcinoma (HCC), in comparison to computed tomography (CT). PATIENTS AND METHODS: Twenty-five consecutive patients with a history of HCC were examined by planar and single-photon emission computed tomography (SPECT) imaging at 6 and 24 hours after intravenous (I.V.) injection of 1 mg AFP-Scan labeled with 925 MBq 99mTc. RESULTS: In 20 patients, there was a specific binding of the Fab' antibody to the tumor, whereas in four patients who presented with elevated serum AFP levels, no specific targeting was found and no malignant lesions were evident by CT or biopsy. One patient was diagnosed as false-negative by AFP-Scan. In five of six patients with normal serum AFP levels, focal uptake was demonstrated. In one case, metastatic disease in the lower abdomen was found. In all patients, diagnostically relevant information was provided by the 24-hour antibody images, especially with SPECT. Comparing AFP-Scan versus CT, the former showed a higher sensitivity (95% v 63%) and specificity (67% v 17%), with an overall accuracy of 88% versus 52% for AFP-Scan versus CT, even in patients with normal serum AFP titers. No adverse reactions or human antimouse antibody (HAMA) elevations were found in any of the patients. CONCLUSIONS: AFP-Scan appears to be a promising new antibody imaging kit for the disclosure of sites of HCC and should aid in the management of these patients by revealing primary, recurrent, and metastatic disease with a single imaging modality.

Is normal gastric emptying a predictor of normal gastric function?

AIM: Impaired gastric emptying is common in many disorders. Assuming that gastric disorders primarily affect gastric peristalsis, which secondarily results in impaired emptying, the aim of our study was to evaluate whether quantitative analysis of gastric peristalsis might be a more sensitive parameter than gastric emptying to demonstrate functional gastric impairment. PATIENTS, METHODS: Gastric emptying was determined scintigraphically in 141 adult (age: 18-78 years) patients (long-term Type 1 diabetes mellitus, 82 cases; systemic sclerosis, 31 cases; atrophic gastritis, 28 cases) and 20 healthy age-matched controls after ingestion of a semiliquid test meal. In addition, gastric peristalsis was evaluated by Fourier analysis of condensed images. RESULTS: Compared to the control persons emptying was delayed in 75/141 patients, regular in 63/141 patients, and accelerated in 3/141 patients. As expected, 81% of patients with delayed emptying presented with diminished gastric contraction amplitudes. However, independent of the aetiology of the underlying disorder, 40/63 patients with regular emptying also exhibited reduced peristalsis. CONCLUSION: Normal gastric emptying does not predict normal gastric function. This assumption is supported by the presence of reduced amplitudes in subgroups of patients with various disorders and normal emptying. Our results suggest that the amplitude of gastric contractions may represent a more sensitive parameter for the detection of gastric dysfunction than does gastric emptying.

Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: A [123 I]ß-CIT SPECT study.

Altered SERT and DAT availabilities during treatment with escitalopram were investigated with [(123)I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane (ß-CIT) SPECT in a series of patients fulfilling the criteria for unipolar major depressive disorder (MDD). 27 patients (10m, 42±16y) with diagnosis of MDD were recruited for the study. All patients underwent neuropsychiatric testing for assessment of Hamilton Depression (HAM-D) and Beck Depression Inventory (BDI) scores. At baseline, [(123)I]ß-CIT SPECT recordings were acquired 4h (SERT-weighted) and 20-24h p.i (DAT-weighted). Follow-up scans and neuropsychiatric testing were performed after six weeks of stable escitalopram medication. Voxel-wise parametric maps of specific/ non-specific ratios-1 (~BPND) were calculated. At baseline, DAT-weighted BPND was 5.06±0.81 in striatum and SERT-weighted BPND was 0.94±0.18 in thalamus. There were significant negative correlations with age for DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under SSRI treatment there was an apparent 42% occupancy of SERT in thalamus (p<0.0001), whereas DAT availability increased significantly by 20% in striatum (p<0.001); higher apparent SERT occupancy in thalamus was associated with lesser DAT increase in striatum (R=-0.62; p<0.005). The low apparent SERT occupancy may be confounded by alterations in SERT expression during treatment. Thus, [(123)I]ß-CIT SPECT revealed age-dependent declines in DAT and SERT availabilities in un-medicated MDD patients, comparable to that seen previously in healthy controls. At follow-up, the SSRI-evoked increase in DAT was less pronounced in the older patients, even though apparent SERT occupancy and clinical improvement were not age-dependent. Present findings may have implications for escitalopram dosage and side effect profile in younger MDD patients.

Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients.

OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis.

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.

Reduced cerebral blood flow in early stages of human immunodeficiency virus infection.

In order to determine if brain perfusion abnormalities, which are known in patients with acquiredimmunodeficiency syndrome dementia, occur in early stages of human immunodeficiency virus infection, technetium 99m hexamethyl-propyleneamine oxime-single-photon emission computed tomography studies were performed in 20 patients infected with human immunodeficiency virus who belonged to Walter Reed stages I through IV. None of these patients demonstrated signs of dementia or severe neurological dysfunction. Pathological patterns of hexamethyl-propyleneamine oxime uptake were seen in 14 patients, seven of whom had normal results during neurological examination. Only four patients had signs of cerebral atrophy on cranial computed tomographic scan. These data suggest that subtle changes in cerebral perfusion seem to arise early in the course of human immunodeficiency virus infection and may indicate human immunodeficiency virus encephalopathy before neurological symptoms or noticeable structural damage occurs.

Cerebral involvement in McLeod syndrome.

McLeod syndrome is an Xp21-linked Kell blood group variant due to lack of erythrocyte protein Kx with associated RBC membrane dysfunction such as acanthocytosis. A man with this syndrome developed chorea and slight neuropsychological impairment. He had caudate atrophy on cerebral imaging and reduced striatal dopamine D2-receptor binding on single-photon emission computed tomography. Since Xp21 was partly deleted in the patient, the missing gene product (possibly Kx) may be essential for the integrity of the striatum.

123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism.

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used in a prospective study to investigate 83 patients with parkinsonism (Hoehn and Yahr stages I to III) who had not been previously treated with dopamimetic drugs. All patients had clinical signs that were compatible with Parkinson's disease. An additional 13 patients had clinical signs of another basal ganglia disorder, such as progressive supranuclear palsy or multisystem atrophy. 123I-IBZM-SPECT results were compared with clinical responses to subcutaneous injections of the D1/D2-receptor agonist apomorphine (83 patients) and to long-term oral dopamimetic therapy (62 patients). Results from 123I-IBZM-SPECT predicted a positive or negative response to apomorphine in 69 of 76 patients (apomorphine responses were equivocal in 7 patients) and a response to dopamimetic therapy in 54 of 62 patients. All patients with a clinical diagnosis of progressive supranuclear palsy or multisystem atrophy had reduced 123I-IBZM binding. In six of these patients, the response to apomorphine was negative, and none clearly benefited from long-term oral levodopa therapy. Imaging of dopamine D2 receptors with 123I-IBZM-SPECT appears to distinguish between patients with de novo parkinsonism that is levodopa-responsive (probably Parkinson's disease of Lewy body type) and that which does not respond to levodopa therapy.

123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism.

We used 123I-iodobenzamide-single photon emission computed tomography (IBZM-SPECT) in a prospective study to investigate 38 patients with parkinsonism (Hoehn and Yahr stage I to III) not previously treated with dopamimetic drugs. Thirty-four patients only showed symptoms of Parkinson's disease, and four patients showed, in addition, subtle clinical signs of progressive supranuclear palsy or multisystem atrophy. IBZM is a dopamine D2 receptor antagonist detectable by SPECT. We compared IBZM-SPECT results with clinical response to subcutaneous injections of the D1/D2 dopamine receptor agonist apomorphine (38 patients) and long-term dopamimetic therapy (31 patients). IBZM-SPECT results predicted a positive or negative response to apomorphine in 30 of 34 patients (apomorphine response in four patients was equivocal) and response to dopamimetic therapy in 27 of 31 patients. Thus, imaging of dopamine D2 receptors using readily available IBZM-SPECT seems to distinguish between L-dopa-responsive (most likely Parkinson's disease of Lewy body type) and L-dopa-unresponsive parkinsonism in patients not previously treated with dopamimetic drugs.

Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome.

Fourteen drug-naive and 11 levodopa-treated patients with idiopathic restless legs syndrome (RLS), and 10 controls age-matched to each RLS group separately were examined with polysomnography (PSG), [(123)I]-(N)-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ((123)I-IPT) SPECT, and [(123)I]-(S)-2-hydroxy-3-iodo-6-methoxy-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide ((123)I-IBZM) SPECT. Drug-naive and levodopa-treated patients with RLS and controls showed similar striatal dopamine transporter and dopamine D(2)-receptor binding, the latter declining with age. The authors conclude that striatal dopamine transporter and receptor density is normal in drug-naive and levodopa-treated patients with RLS.

Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease.

We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C-raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons.

Multiple swallow test for the quantitative and qualitative evaluation of esophageal motility disorders.

Esophageal motility was evaluated from the analysis of six consecutive swallows. A sum image was generated comprising the representative information of an entire study. Calculation of emptying rates and characterization of the bolus behavior was performed from the sum image and the single swallow data. In 86 patients investigated, liquid and solid-phase studies showed a remarkable variation of single swallow data in normals (relative variation coefficient for liquid: 10%, solid: 14%), which were even higher (p less than 0.001) in patients with disorders (liquid: 31%, solid: 25%). As sum images compensate for this intra-individual variation, false-positive (liquid: 16%, solid: 25%) or negative single swallow findings (liquid: 36%, solid: 27%) are reduced. Qualitative analysis of condensed sum images provided characteristic image patterns representing different pathophysiologic aspects. Since the method introduced better discriminates between normal and pathologic function, it may enhance diagnostic accuracy.

Iodine-123-iodobenzamide binding in parkinsonism: reduction by dopamine agonists but not L-Dopa.

UNLABELLED: The aim of the present study was to investigate the effect of treatment with L-Dopa or a dopamine agonist, or both, on specific striatal 123I-iodobenzamide (IBZM) binding using an intraindividual longitudinal design. METHOD: We prospectively studied the effect of dopaminomimetic treatment on specific [123I]IBZM binding measured by SPECT in 29 patients with a clinical diagnosis of Parkinson's disease, none of whom had previously received dopaminomimetic drugs. The patients had been selected on the basis of normal subsequent specific [123I]IBZM binding, semiquantitatively calculated as the basal ganglia/frontal cortex ratio, and a positive response to the dopamine agonist apomorphine before initiation of dopaminomimetic therapy. A second 123I-IBZM SPECT investigation was performed after 3-6 mo of treatment with L-Dopa or a dopamine agonist, or both. RESULTS: Specific [123I]IBZM binding was unchanged in 10 patients treated with L-Dopa alone. However, after treatment with a dopamine agonist there was a significant decline in specific [123I]IBZM binding (p < 0.05). After treatment with a combination of L-Dopa and a dopamine agonist, specific [123I]IBZM binding was reduced without reaching a level of significance (p = 0.08). CONCLUSION: Short-term treatment with a dopamine agonist but not with L-Dopa reduces specific [123I]IBZM binding. Therefore, before performing an [123I]IBZM SPECT scan in patients previously treated with dopaminomimetic drugs, dopamine agonists should be discontinued.

Optimization of automated quantification of 123I-IBZM uptake in the striatum applied to parkinsonism.

UNLABELLED: Evaluation of therapies for parkinsonism by dopamine receptor SPECT requires a reproducible, optimized quantitation technique. This study presents a new, objective, automated technique for semiquantitative analysis of dopamine receptor density, as applied to the differential diagnosis of parkinsonism. METHODS: Dopamine receptor density measured by 123I-iodobenzamide (IBZM) SPECT was retrospectively analyzed in nonidiopathic parkinsonism (NIPS), in Parkinson's disease (PD), and in healthy volunteers (n = 19, 38, and 13, respectively). A mean template was created from coregistered control studies. Registration errors were assessed using studies with simulated binding deficits. Patient studies were registered to the mean template, and striatal binding was calculated from a corresponding map of 3-dimensional regions of interest (ROIs). The striatal binding ratio and deficits determined by voxelwise comparison with the normal template were investigated and tested with various 3-dimensional ROI sizes and positions. Separation of patient groups was determined by tscore after automatically processing all studies. Results were compared with manual ROI analyses. RESULTS: The automatic method was completely reproducible in 64 of 70 cases. The best diagnostic discriminator was the minimum binding ratio of the 2 striatal nuclei, with the following values: NIPS, 1.33+/-0.13; PD, 1.50+/-0.12; healthy volunteers, 1.49+/-0.08 (+/-SD). The deficit size from voxelwise analysis was: NIPS, 20.5+/-8.2 mL; PD, 9.5+/-8.3; healthy volunteers, 8.9+/-6.0 (+/-SD). The accuracy, measured by receiver operating characteristic areas, was 0.85+/-0.05, 0.77+/-0.06, and 0.80+/-0.06 (+/-SE) for the optimal predictor (automated) and 2 blinded observers (manual), respectively. CONCLUSION: A new 3-dimensional, automated technique has been developed to semiquantitate receptor density that dramatically improves reproducibility. The optimal diagnostic discriminator of parkinsonism determined by the automatic technique has good accuracy compared with the manual technique.