Automated analysis of FDG PET as a tool for single-subject probabilistic prediction and detection of Alzheimer's disease dementia.

PURPOSE: To introduce, evaluate and validate a voxel-based analysis method of ¹8F-FDG PET imaging for determining the probability of Alzheimer's disease (AD) in a particular individual. METHODS: The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis. RESULTS: The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8% to 100% in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95% CI 0.646 - 0.838), but this increased to 0.804 (95% CI 0.714 - 0.894, bootstrap p=0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7% of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75% in the high probability group (sixtile 6), 34% in the medium probability group (merged sixtiles 4 and 5), 20% in the low probability group (sixtile 3) and 7.5% in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95% CI 0.625 - 0.969) and the AD-Conv score reached 0.968 (95% CI 0.908 - 1.000), with AD patients and MCI converters included in the highest probability categories. CONCLUSION: Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.

Quantitative volumetric analysis of gliomas with sequential MRI and ¹¹C-methionine PET assessment: patterns of integration in therapy planning.

PURPOSE: The aim of the study was to evaluate the volumetric integration patterns of standard MRI and (11)C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. METHODS: We studied 23 patients with suspected or previously treated glioma who underwent preoperative (11)C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by (11)C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. RESULTS: Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high (11)C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p < 0.001, κ = 0.72). GBM was associated with pattern vMRI-in-vPET (9/10), low-grade with pattern vPET-in-vMRI (7/8) and anaplastic with pattern vMRI-diff-vPET (3/5). CONCLUSION: The metabolically active tumour volume observed in (11)C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in (11)C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas.

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain.

BACKGROUND: The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacro-iliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. METHODS: Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. RESULTS: The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. CONCLUSION: Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quanti-tative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.

Variation of enterohepatic circulation observed with 75SeHCAT images in the first three hours. Scintigraphic patterns and analysis of their association with the diagnosis of bile acid malabsorption.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 h and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1-3 h determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 h, 2) gallbladder 3 h, 3) gallbladder-abdomen 2-3 h, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7 > 15%), mild-BAM (AR7 15-10%), moderate-BAM (AR7 10-5%) or severe-BAM (AR7 < 5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 h" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 h" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 h were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Variation of enterohepatic circulation through the image with 75SeHCAT in the first 3 hours. Scintigraphic patterns and análisis of its association with the diagnosis of bile acid malabsorption. / Variación de la circulación enterohepática a través de la imagen con 75SeHCAT en las 3 primeras horas. Patrones gammagráficos y análisis de su asociación con el diagnóstico de malabsorción de ácidos biliares.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 hours and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1 to 3 hours determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 hours, 2) gallbladder 3 hours, 3) gallbladder-abdomen 2-3 hours, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7>15%), mild-BAM (AR7: 15-10%), moderate-BAM (AR7: 10-5%) or severe-BAM (AR7<5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 hours" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 hours" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 hours were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Field camera versus phantom-based measurement of the gradient system transfer function (GSTF) with dwell time compensation.

PURPOSE: The gradient system transfer function (GSTF) can be used to describe the dynamic gradient system and applied for trajectory correction in non-Cartesian MRI. This study compares the field camera and the phantom-based methods to measure the GSTF and implements a compensation for the difference in measurement dwell time. METHODS: The self-term GSTFs of a MR system were determined with two approaches: 1) using a dynamic field camera and 2) using a spherical phantom-based measurement with standard MR hardware. The phantom-based GSTF was convolved with a box function to compensate for the dwell time dependence of the measurement. The field camera and phantom-based GSTFs were used for trajectory prediction during retrospective image reconstruction of 3D wave-CAIPI phantom images. RESULTS: Differences in the GSTF magnitude response were observed between the two measurement methods. For the wave-CAIPI sequence, this led to deviations in the GSTF predicted trajectories of 4% compared to measured trajectories, and residual distortions in the reconstructed phantom images generated with the phantom-based GSTF. Following dwell-time compensation, deviations in the GSTF magnitudes, GSTF-predicted trajectories, and resulting image artifacts were eliminated (< 0.5% deviation in trajectories). CONCLUSION: With dwell time compensation, both the field camera and the phantom-based GSTF self-terms show negligible deviations and lead to strong artifact reduction when they are used for trajectory correction in image reconstruction.

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification.

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.

[Quick and simple synthesis of (11)C-(+)-alpha-dihydrotetrabenazine to be used as a PET radioligand of vesicular monoamine transporters]. / Síntesis rápida y simplificada de C-(+)-alpha-dihidrotetrabenazina para su utilización como radioligando PET de los transportadores vesiculares de monoaminas.

UNLABELLED: Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. OBJECTIVE: To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivo studies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). MATERIALS AND METHODS: We have developed a new fully automated synthesis procedure to obtain 11C-(+)DTBZ quickly and simply through labelling the precursor -(+)desmethyldihy-drotetrabenazine- at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11CH3I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. RESULTS: The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen-free 11C-(+)DTBZ with a radiochemical purity > 99 % was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11CH3I production. 11C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularis monkeys. CONCLUSIONS: This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.

[Use of 11C-(+)-alpha -dihydrotetrabenazine for the assessment of dopaminergic innervation in animal models of Parkinson's disease]. / Utilización de la 11C-(+)-alpha -dihidrotetrabenazina para la evaluación de la inervación dopaminérgica en modelos animales de la enfermedad de Parkinson.

AIM: This study evaluates the utility of (11)C-(+)-alpha -dihydrotetrabenazine ((11)C-(+)DTBZ) in the quantification of dopaminergic innervation by positron emission tomography (PET) in rat and monkey, two animal species used as animal models of Parkinson's disease. MATERIAL AND METHODS: Healthy control animals (n = 10) and the effect of 6-hydroxidopamine (6-OHDA) neurotoxic were studied in rats. (18)F-DOPA PET studies and digital quantitative autoradiography were also carried out. Studies with Macaca fascicularis were performed in control and 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP) treated animals. RESULTS: In both species high quality images were generated in which clear uptake of (11)C-(+)DTBZ was found in the striatum. (11)C-(+)DTBZ uptake quantification was estimated by creating parametric images and binding potential (BP) calculation. BP in control rats was 1.10 +/- 0.16 (mean +/- standard deviation [SD], whereas 6-OHDA produced a decrease in the uptake depending on the lesion degree. Images obtained with (18)F-DOPA were not adequate for the analysis as they did not discriminate the stratum whereas digital quantitative autoradiography studies confirmed the high affinity of striatum by (11)C-(+)DTBZ. In monkeys, final BP values were 1.31 and 1.06 and MPTP treatment reduced uptake by 40 %. CONCLUSIONS: The quality of PET images and the decrease of uptake in 6-OHDA and MPTP lesions show that (11)C-(+)DTBZ is an adequate radiotracer for the study of dopaminergic innervation in these animal models.

[New horizons in breast surgery. Radioguided surgery and selective sentinel node biopsy]. / Nuevos horizontes en cirugía mamaria. Cirugía radioguiada y biopsia selectiva de ganglio centinela.

Although needle-wire localization is the most commonly used localization technique for nonpalpable breast lesion biopsy, the technique of radioguided occult lesion localization (ROLL), is becoming increasingly used for open-surgery diagnosis in such cases. Sentinel lymph node biopsy(SLNB) is based on the hypothesis that lymphatic drainage from a tumor reaches the sentinel node(SLN) first and that it can be identified accurately and removed. If SLN exactly reflects the lymph-node status, a negative SLN for metastasis might allow complete axillary lymph node dissection (ALDN) to be avoided.

[Positron emission tomography in breast cancer]. / Tomografía por emisión de positrones en el cáncer de mama.

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer.

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis.

UNLABELLED: Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. AIMS: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. ANIMALS, METHODS: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. RESULTS: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p < 0.05) that persisted throughout the study. Semiquantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p < 0.001). CONCLUSION: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.

Radiation dose produced by patients during radiopharmaceutical incorporation in nuclear medicine diagnostic procedures.

OBJECTIVES: The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. MATERIAL AND METHODS: A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). RESULTS: During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 µSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. CONCLUSION: It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.

Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [(18)F]-tetrafluoroborate.

BACKGROUND: [(18)F]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99m)Tc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [(18)F]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs. METHODS: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 ± 0.05 MBq/kg of [(18)F]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [(18)F]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model. RESULTS: [(18)F]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the organs that express NIS (stomach wall, salivary glands, thyroid, olfactory mucosa), are involved in excretion (kidneys and bladder), or reflect the vascular phase (heart and lungs). Considering the OLINDA source organs, the critical organs were the stomach wall, thyroid and bladder wall, with absorbed doses lower than 0.078 mGy/MBq. The effective dose was 0.025 mSv/MBq. CONCLUSIONS: [(18)F]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99m)Tc-pertechnetate but much lower than that produced by radioiodine in the form of (131)INa, (123)INa, or (124)INa.

Increased release of [3H]acetylcholine in vitro from the mouse hippocampus by a convulsant barbiturate.

The effects of the convulsant barbiturate, 5-(2-cyclohexylidene-ethyl)-5-ethyl barbituric acid (CHEB), on the spontaneous release of [3H]acetylcholine (ACh) from mouse hippocampal slices in an in vitro superfusion system have been evaluated. The pattern of the release of [3H]ACh by a single treatment with CHEB or an elevated potassium concentration was similar, with the peak release occurring in the same fraction. A maximally effective concentration of CHEB (500 microM) caused a 177% stimulation of spontaneous release of [3H]ACh, while 50 mM KCl increased the release by 2100% above the baseline. The stimulation of the spontaneous release of [3H]ACh by CHEB was concentration-dependent with an EC50 of 180 microM. The pattern of release of [3H]ACh induced by multiple treatment with CHEB and elevated potassium appeared to differ, suggesting that different pools of [3H]ACh in the cholinergic neurons might be affected by these treatments. The action of CHEB on the spontaneous release of [3H]ACh was unique among some other convulsant drugs that were studied. Another convulsant barbiturate, S(+)-1-methyl-5-phenyl-5-propyl barbituric acid [S(+)-MPPB], pentylenetetrazol and a convulsant benzodiazepine 1,3-dihydro-5-methyl-2H-1,4-benzodiazepine-2-one (Ro-5-3663) did not affect the spontaneous release of [3H]ACh. The relationship between the stimulation of release of ACh and the convulsant action of the barbiturates is discussed.

The effects of an in vivo administration of phencyclidine on sodium-dependent high affinity choline uptake in rat hippocampus and striatum in vitro.

The effect of phencyclidine and other drugs on sodium-dependent high-affinity uptake of choline in the rat hippocampus and/or striatum was investigated and related to the behavioral changes induced by these agents. In contrast to atropine (40.0 mg/kg), which increased the uptake of choline in synaptosomes from both the rat hippocampus and striatum, the administration of phencyclidine (54.4 mg/kg), 30 min prior to sacrifice, caused a significant decrease in the uptake of choline in synaptosomes from rat striatum (but not hippocampus). This effect of phencyclidine could be seen up to 1 hr after administration of drug, but by 3.5 hr the uptake of choline was essentially back to normal. The inhibition of striatal uptake of choline occurred at a time when brain levels of phencyclidine and its metabolites were at their highest, and the animals were essentially immobile; it did not appear to correlate with behavioral changes (including stereotypy and catalepsy) seen at later times after this dose of phencyclidine (54.4 mg/kg), or at earlier times after smaller doses. Amphetamine (6.0 mg/kg) also decreased the uptake of choline in the striatum. Haloperidol (2.0 and 3.0 mg/kg) blocked both the phencyclidine and amphetamine-induced inhibition of the uptake of choline but only the behavioral effects of amphetamine. The data suggest that phencyclidine may be exerting an indirect effect on the uptake of choline in the striatum via its interaction with the dopaminergic system. However, this neurochemical effect of phencyclidine could not be related in any simple way to the immobility, stereotypy or catalepsy caused by this drug.

Three-dimensional clinical PET in lung cancer: validation and practical strategies.

UNLABELLED: The feasibility of 3-dimensional acquisition mode for semiquantitative analysis in thoracic PET studies was compared to the conventional 2-dimensional mode. Several practical considerations were analyzed to propose an optimized scanning protocol for clinical use. METHODS: Twenty-one patients with focal thoracic abnormalities were evaluated with FDG PET. The acquisition consisted of 3 consecutive static scans for a single bed position: 3-dimensional (10 min), 2-dimensional (15 min), and 3-dimensional (5 min). On the basis of the average and maximum activity values per region of interest, standardized uptake value (SUV) normalized for total body weight (TBW), lean body mass (LBM), body surface area (BSA), and blood glucose level (PGL) were evaluated. The effect of the delay between tracer injection and PET scanning on the SUV, as well as on the relative error of the activity distribution, was studied from 40-134 min after tracer injection. RESULTS: A strong positive correlation was observed among SUVs from 2-dimensional and both 3-dimensional acquisitions. The mean SUV percentage differences between both acquisition modes were about 17%, differences that were not statistically significant when time postinjection was addressed in the analysis of covariance. SUVs provided the greatest variability and differences among studies on experimental periods up to 70 min postinjection. Indeed, the variability of 20% observed on the SUVs from 2 PET scans 13 min apart was reduced to 9% when the acquisitions started at least 70 min after tracer injection. In addition, a two-fold reduction in the relative error of the activity distribution was observed over this period of time. The reproducibility coefficient was increased from 0.87 to 0.95 before and after 70 min postinjection, respectively. No correlation was found between different normalization procedures of SUV and LBM, BSA, TBW, or height, whereas a weak correlation was found between SUV and PGL. CONCLUSION: 18F-FDG 3-dimensional PET is a realistic alternative to the gold standard 2-dimensional for clinical nonkinetic studies. A short, 5-min 3-dimensional acquisition at 70 min postinjection is proposed as the best protocol for the clinical evaluation of thoracic pathologies.

Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes.

The effects of several anticonvulsant drugs on sodium-dependent high affinity choline uptake (HACU) in mouse hippocampal synaptosomes was investigated. HACU was measured in vitro after in vivo administration of the drug to mice. HACU was inhibited by drugs which have in common the ability to facilitate gamma-aminobutyric acid (GABA) transmission, pentobarbitone, phenobarbitone, barbitone, diazepam, chloridiazepoxide, and valproic acid. Dose-response relationships were determined for these drugs and the drugs' potencies at inhibiting HACU correlated well with their anticonvulsant potencies. Clonazepam, ethosuximide, carbamazepine, and barbituric acid had no effect on HACU in the doses used while phenytoin and trimethadione stimulated HACU. These results suggest that certain anticonvulsants may elicit a part of their anticonvulsant activity by modulating cholinergic neurones. This effect may be mediated through a GABA mechanism.

Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations.

The efficacy of aprotinin to reduce intraoperative bleeding tendency in cardiac operations has been demonstrated in several studies. Aprotinin is a polybasic polypeptide and has antigenic properties. Anaphylactic reactions to aprotinin have been described. The aim of the present study was to evaluate the prevalence of adverse reactions to reexposure to high-dose aprotinin. The clinical outcome of all patients undergoing heart operations in our institution between 1988 and 1995 with at least two exposures to aprotinin was investigated. There were 248 reexposures to aprotinin in 240 patients: 101 adult and 147 pediatric cases. The total aprotinin doses were 4.9 x 10(6) (interquartile range 2 x 10(6)) KIU (adults) and 1.3 x 10(6) (interquartile range 1.2 x 10(6)) KIU (pediatric patients). The time between the first and second aprotinin exposures was 344 (interquartile range 1039) days. Seven adverse reactions to aprotinin were found (2.8%). The severity of the reaction ranged from mild (no intervention) to severe (longer-lasting circulatory depression despite vasopressor therapy). All patients survived the event. Patients with an interval less than 6 months since the previous exposure had a statistically higher incidence of adverse reactions than patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two patients reacted to a test dose of 10,000 KIU aprotinin. Pretreatment with antihistaminics was done in 60% of the patients. We recommend the following procedure for reexposure with high-dose aprotinin: (1) delay of the first bolus injection of aprotinin until the surgeon is ready to begin cardiopulmonary bypass, (2) test dose of 10,000 KIU aprotinin in all patients with aprotinin treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance of reexposure within the first 6 months after the previous exposure to aprotinin. With these precautions a reexposure to aprotinin in patients with a high risk of bleeding is justified, because the benefits of aprotinin treatment outweigh the relative risk of a serious allergic reaction.