Introducing a gatekeeping system for amyloid status assessment in mild cognitive impairment.

BACKGROUND: In patients with mild cognitive impairment (MCI), enhanced cerebral amyloid-ß plaque burden is a high-risk factor to develop dementia with Alzheimer's disease (AD). Not all patients have immediate access to the assessment of amyloid status (A-status) via gold standard methods. It may therefore be of interest to find suitable biomarkers to preselect patients benefitting most from additional workup of the A-status. In this study, we propose a machine learning-based gatekeeping system for the prediction of A-status on the grounds of pre-existing information on APOE-genotype 18F-FDG PET, age, and sex. METHODS: Three hundred and forty-two MCI patients were used to train different machine learning classifiers to predict A-status majority classes among APOE-ε4 non-carriers (APOE4-nc; majority class: amyloid negative (Aß-)) and carriers (APOE4-c; majority class: amyloid positive (Aß +)) from 18F-FDG-PET, age, and sex. Classifiers were tested on two different datasets. Finally, frequencies of progression to dementia were compared between gold standard and predicted A-status. RESULTS: Aß- in APOE4-nc and Aß + in APOE4-c were predicted with a precision of 87% and a recall of 79% and 51%, respectively. Predicted A-status and gold standard A-status were at least equally indicative of risk of progression to dementia. CONCLUSION: We developed an algorithm allowing approximation of A-status in MCI with good reliability using APOE-genotype, 18F-FDG PET, age, and sex information. The algorithm could enable better estimation of individual risk for developing AD based on existing biomarker information, and support efficient selection of patients who would benefit most from further etiological clarification. Further potential utility in clinical routine and clinical trials is discussed.

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase biomarker development framework.

PURPOSE: In 2017, the Geneva Alzheimer's disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [18F]flortaucipir PET and define its research priorities. METHODS: The level of maturity of [18F]flortaucipir was assessed based on the AD Biomarker Roadmap. The framework assesses analytical validity (phases 1-2), clinical validity (phases 3-4), and clinical utility (phase 5). RESULTS: The main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. [18F]Flortaucipir binds with high affinity to paired helical filaments of tau and has favorable kinetic properties and excellent discriminative accuracy for AD. The majority of secondary aims of phase 2 were fully achieved. Multiple studies showed high correlations between ante-mortem [18F]flortaucipir PET and post-mortem tau (as assessed by histopathology), and also the effects of covariates on tracer binding are well studied. The aims of phase 3 (early detection ability) were only partially or preliminarily achieved, and the aims of phases 4 and 5 were not achieved. CONCLUSION: Current literature provides partial evidence for clinical utility of [18F]flortaucipir PET. The aims for phases 1 and 2 were mostly achieved. Phase 3 studies are currently ongoing. Future studies including representative MCI populations and a focus on healthcare outcomes are required to establish full maturity of phases 4 and 5.

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework.

PURPOSE: In the last decade, the research community has focused on defining reliable biomarkers for the early detection of Alzheimer's disease (AD) pathology. In 2017, the Geneva AD Biomarker Roadmap Initiative adapted a framework for the systematic validation of oncological biomarkers to cerebrospinal fluid (CSF) AD biomarkers-encompassing the 42 amino-acid isoform of amyloid-ß (Aß42), phosphorylated-tau (P-tau), and Total-tau (T-tau)-with the aim to accelerate their development and clinical implementation. The aim of this work is to update the current validation status of CSF AD biomarkers based on the Biomarker Roadmap methodology. METHODS: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of CSF AD biomarkers was assessed based on the Biomarker Roadmap methodology before the meeting and presented and discussed during the workshop. RESULTS: By comparison to the previous 2017 Geneva Roadmap meeting, the primary advances in CSF AD biomarkers have been in the area of a unified protocol for CSF sampling, handling and storage, the introduction of certified reference methods and materials for Aß42, and the introduction of fully automated assays. Additional advances have occurred in the form of defining thresholds for biomarker positivity and assessing the impact of covariates on their discriminatory ability. CONCLUSIONS: Though much has been achieved for phases one through three, much work remains in phases four (real world performance) and five (assessment of impact/cost). To a large degree, this will depend on the availability of disease-modifying treatments for AD, given these will make accurate and generally available diagnostic tools key to initiate therapy.

The validation status of blood biomarkers of amyloid and phospho-tau assessed with the 5-phase development framework for AD biomarkers.

PURPOSE: The development of blood biomarkers that reflect Alzheimer's disease (AD) pathophysiology (phosphorylated tau and amyloid-ß) has offered potential as scalable tests for dementia differential diagnosis and early detection. In 2019, the Geneva AD Biomarker Roadmap Initiative included blood biomarkers in the systematic validation of AD biomarkers. METHODS: A panel of experts convened in November 2019 at a two-day workshop in Geneva. The level of maturity (fully achieved, partly achieved, preliminary evidence, not achieved, unsuccessful) of blood biomarkers was assessed based on the Biomarker Roadmap methodology and discussed fully during the workshop which also evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers. RESULTS: Plasma p-tau has shown analytical validity (phase 2 primary aim 1) and first evidence of clinical validity (phase 3 primary aim 1), whereas the maturity level for Aß remains to be partially achieved. Full and partial achievement has been assigned to p-tau and Aß, respectively, in their associations to ante-mortem measures (phase 2 secondary aim 2). However, only preliminary evidence exists for the influence of covariates, assay comparison and cut-off criteria. CONCLUSIONS: Despite the relative infancy of blood biomarkers, in comparison to CSF biomarkers, much has already been achieved for phases 1 through 3 - with p-tau having greater success in detecting AD and predicting disease progression. However, sufficient data about the effect of covariates on the biomarker measurement is lacking. No phase 4 (real-world performance) or phase 5 (assessment of impact/cost) aim has been tested, thus not achieved.

Value of bone marrow biopsy in Hodgkin lymphoma patients staged by FDG PET: results from the German Hodgkin Study Group trials HD16, HD17, and HD18.

Background: Bone marrow (BM) involvement defines advanced-stage Hodgkin lymphoma and thus has impact on the assignment to treatment. Our aim was to evaluate whether the established BM biopsy may be omitted in patients if 18F-fluorodeoxyglucose positron emission tomography (PET) scanning is carried out during staging. Patients and methods: Our analysis set consisted of 832 Hodgkin lymphoma patients from the German Hodgkin Study Group trials HD16, HD17, and HD18 who underwent both PET scanning and BM biopsy before treatment. All PET studies were centrally reviewed and BM was categorized as showing focal involvement or not. Results: Taking BM biopsy as reference standard, baseline PET showed a negative predictive value of 99.9% [95% confidence interval (CI) 99.2% to 100%] with true-negative results in 702 of 703 cases. The sensitivity of PET for detecting BM involvement was 95.0% (95% CI 75.1% to 99.9%) as it could identify 19 out of 20 patients with positive BM biopsy. Moreover, PET found 110 additional subjects with focal BM lesions who would have been considered negative by biopsy. Conclusions: When compared with BM biopsy, PET was able to detect focal BM lesions in a large number of additional patients. This indicates that conventional BM biopsy may substantially underestimate the actual incidence of BM involvement. Given the high negative predictive value, baseline PET scanning can safely be used to exclude BM involvement in Hodgkin lymphoma. BM biopsy should be considered only in such patients in whom PET-detected lesions lead to a change of treatment protocol. Registered trials: The trials included in this analysis were registered at ClinicalTrials.gov: HD16-NCT00736320, HD17-NCT01356680, and HD18-NCT00515554.

European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain 18 F-fluorodeoxyglucose positron emission tomography in neurodegenerative cognitive impairment and dementia: Delphi consensus.

BACKGROUND AND PURPOSE: Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured. METHODS: Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion. RESULTS: Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline. CONCLUSIONS: Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.

[The importance of molecular imaging (PET) in the diagnostics of dementia]. / Bedeutung molekularer Bildgebung (PET) in der Diagnostik von Demenzerkrankungen.

Due to the expanding older population and increasing prevalence of dementia and currently lacking curative therapy but potentially conceivable availability of molecular-specific treatment to delay the progression of cognitive decline, the early diagnosis of cognitive deficits and their etiological differential diagnosis becomes increasingly more important. The advances in nuclear medicine diagnostics in the field of neurodegenerative diseases within the last few years have been substantial. In this article the relevance of these technologies in the diagnostic process of dementia is described.

Current status and future role of brain PET/MRI in clinical and research settings.

Hybrid PET/MRI systematically offers a complementary combination of two modalities that has often proven itself superior to the single modality approach in the diagnostic work-up of many neurological and psychiatric diseases. Emerging PET tracers, technical advances in multiparametric MRI and obvious workflow advantages may lead to a significant improvement in the diagnosis of dementia disorders, neurooncological diseases, epilepsy and neurovascular diseases using PET/MRI. Moreover, simultaneous PET/MRI is well suited to complex studies of brain function in which fast fluctuations of brain signals (e.g. related to task processing or in response to pharmacological interventions) need to be monitored on multiple levels. Initial simultaneous studies have already demonstrated that these complementary measures of brain function can provide new insights into the functional and structural organization of the brain.

[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.

[Visualization of amyloid with positron emission tomography. Useful improvement in the diagnosis of dementia?]. / Amyloiddarstellung mittels Positronenemissionstomographie. Ein nützlicher Fortschritt in der Demenzdiagnostik?

Imaging techniques for in vivo visualization of cerebral amyloid using positron emission tomography (PET) have been tested in clinical trails over the past 5 years. Based on a selected overview of the literature including our own studies the various radiopharmaceuticals are presented and the current status of research on the validity of amyloid PET imaging as well as its suitability for early and differential diagnosis of Alzheimer's disease (AD) are described. The findings available up to now support the validity of amyloid PET imaging and suggest a possible benefit in differential diagnosis. However, there are as yet no studies with large sample sizes. The possible use for the early diagnosis of AD should be viewed critically, particularly due to the lack of treatment options.

Combined Early and Late [68Ga]PSMA-HBED-CC PET Scans Improve Lesion Detectability in Biochemical Recurrence of Prostate Cancer with Low PSA Levels.

PURPOSE: Our aim was to evaluate the benefit of early (1 h post-injection (p.i.)) and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of prostate cancer (PCa). PROCEDURES: Seventy patients with BCR of the PCa and prostate-specific antigen (PSA) levels of less than 2.0 µg/l were subjected to [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging contained whole body scans, late imaging was confined to the pelvis and the lower abdomen. Uptake in suspicious lesions was analyzed by peak and maximum standardized uptake values (SUVpeak/max). Tumor-to-background ratios were calculated for all lesions in which the liver served as reference organ. The Wilcoxon matched-pair signed-rank test was used to compare the uptake in suspicious lesions between early and late imaging. Follow-up data were used to validate the existence of the additionally detected lesions. RESULTS: Forty-four of the 70 patients thus examined were interpreted as PSMA-positive in early and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from seven different patients were better or exclusively visible in the late measurements while three tumor-suspicious lesions from three different patients were better or exclusively visible in the early images. A validation by follow-up data was possible for 11 of these 13 additionally detected lesions. In direct comparison between early and late imaging, the mean SUVmax in PSMA-positive lesions was 74 % higher (p < 0.001) and the mean SUVpeak was 36 % higher (p = 0.001) in the late scans. The SUVmean in the reference regions was decreasing in the late measurements, whereas the mean TBR increased by a factor of 3 (p < 0.001). Taking confirmed lesions only into account, we estimated a 10 % gain in additionally detected PSMA-positive lesions (7/70) within the patient cohort. CONCLUSIONS: The time period between injection and data acquisition influences the detection rate of [68Ga]PSMA-HBED-CC PET/CT. In biochemical recurrence with low PSA levels, late [68Ga]PSMA-HBED-CC PET/CT imaging offers frequent advantages with regard to lesion contrast.

CSF total and phosphorylated tau protein, regional glucose metabolism and dementia severity in Alzheimer's disease.

BACKGROUND AND PURPOSE: We investigated associations between severity of cognitive impairment, cerebrospinal fluid (CSF) concentrations of total-tau (t-tau) protein and tau phosphorylated at threonin 181 (p-tau(181)) and regional glucose metabolism measured with 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) in patients with probable Alzheimer's disease (AD). METHODS: In 38 patients (mean age 66.5 +/- 8.0 years) with AD, Mini-Mental State Examination (MMSE) scores were evaluated and CSF levels of t-tau and p-tau(181) measured. All patients underwent an 18F-FDG-PET scan. Image analysis including correlation analysis and principal component analysis (PCA) were performed using SPM5 and VINCI. RESULTS: Dementia severity (MMSE 21.2 +/- 4.9) correlated well with metabolic impairment especially in left hemisphere association areas that are typically affected in patients with AD (e.g. inferior parietal lobule, r = 0.512; medial temporal gyrus, r = 0.478; inferior temporal gyrus, r = 0.488; precuneus, r = 0.468; PCA: r = 0.639, F = 7.751; all P < 0.001). There were no associations between t-tau and p-tau(181) with dementia severity and only weak correlations between t-tau and cerebral glucose metabolism (superior parietal gyrus, r = -0.325, P < 0.05; precentral gyrus r = -0.418, P < 0.01; amygdala r = -0.362, P < 0.05). No correlations were found between p-tau(181) and regional hypometabolism in FDG-PET. CONCLUSION: MMSE and CSF t-tau represent different aspects of disease severity. Whilst MMSE is closely related to impaired cerebral glucose metabolism, CSF t-tau is less closely related and appears to be less well suited for assessment of disease progression.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. / Lutetium-177-PSMA-Radioligandentherapie : Konsensus im Rahmen der GKV-finanzierten Versorgung zwischen den Hochschulkliniken in Aachen, Bonn, Düsseldorf, Essen und Köln und dem MDK Nordrhein.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

Gender differences in brain reserve : an (18)F-FDG PET study in Alzheimer's disease.

BACKGROUND: Neuropathological studies suggest that the association between neurodegenerative brain damage and clinical symptoms may be stronger in women than in men. OBJECTIVE: To test the hypothesis that cerebral metabolic deficits due to neurodegeneration are more pronounced in men than in women at the same level of clinical disease severity. METHODS: 93 patients with mild Alzheimer's disease (AD; 50 men, 43 women) underwent an extensive clinical and neuropsychological examination and (18)F-FDG PET imaging at a university-based outpatient unit for cognitive disorders. An analysis of covariance (with age, total score of the CERAD neuropsychological battery, and years of school education as covariates) was conducted in each study group to identify gender differences in glucose metabolism. RESULTS: Controlling for age, education, and clinical severity, cortical regions were identified,where glucose metabolism was significantly reduced in men as compared with women. These regions were located in areas typically affected by AD pathology (right inferior frontal, superior temporal and insular cortex, and hippocampus). CONCLUSIONS: These data suggest that the same clinical severity of dementia is associated with greater reductions in cerebral metabolism in men than in women suggesting a greater degree of brain reserve in men.

The effectiveness of wastewater treatment in nuclear medicine: Performance data and radioecological considerations.

For planned and ongoing storage of liquid radioactive waste in a designated plant for a nuclear medicine therapy ward (decontamination system/decay system), detailed knowledge of basic parameters such as the amount of radioactivity and the necessary decay time in the plant is required. The design of the plant at the Department of Nuclear Medicine of the University of Cologne, built in 2001, was based on assumptions about the individual discharge of activity from patients, which we can now retrospectively validate. The decontamination factor of the plant is at present in the order of 10-9 for 131I. The annual discharges have been continuously reduced over the period of operation and are now in the region of a few kilobecquerels. This work emphasizes the high efficacy of the decontamination plant to reduce the amount of radioactivity released from the nuclear medicine ward into the environment to almost negligible levels.

Exhalation of 131I after radioiodine therapy: Dosimetric considerations based on measurements in exhaled air.

It is well known that a considerable amount of radioiodine is exhaled after radioiodine therapy (RIT) leading to unwanted radiation exposure through inhalation for non-involved persons. This study focuses on the amount of exhalation in the breath-out air of RIT-patients and the dosimetric consequences. Furthermore, the correlation between radioiodine uptake and exhalation was investigated. The radioiodine species were collected in a filter system and quantified over time by measurements with a scintillation counter. The dosimetric implications were then studied for different exposure scenarios. Of the activity administered to the patient, approximately 10-3% (50-110 ppm) is exhaled. The radioiodine inhalation taking place following exhalation in the vicinity yields doses of up to 500 µSv (children, staying with the patient immediately after application and for the next 8 h). Three days after administration the doses are significantly reduced. This study lays emphasis on previous assumptions that exhalation depends on thyroid storage. Regardless of the type of thyroid disease, the predominant form exhaled is organic radioiodine. The amount of exhaled radioiodine is small but from the point of view of radiation protection, by no means negligible immediately after administration. Radiation doses received by incorporation of exhaled radioiodine can easily exceed 100 µSv soon after administration of radioiodine. Three days after RIT the radioactivity can still be measured in the exhaled air but even at maximum, the annual doses lie far below 10 µSv and are thus comparatively low.

Influence of iodine supply on the radiation-induced DNA-fragmentation.

The protective effect of stable iodide against radiation on thyroid cells was investigated. One physiological effect of stable iodine is well-rooted: stable iodine leads to a reduced thyroid uptake of radioactive iodine. This work wants to focus on an intrinsic effect of stable iodine by which DNA-damage in cells is prevented. To investigate this intrinsic effect thyroid cells (FRTL-5) were externally irradiated by use of a linear accelerator (LINAC) applying energy doses of 0.01 Gy-400 Gy and by incubation with various activity concentrations of 131I (0.1-50 MBq/ml for 24 h). We added stable iodine (NaI) to the cells prior to external irradiation and investigated the effect of the concentration of stable iodine (1, 5, 15 µg/ml). In order to clarify whether thyroid cells have a distinctive and iodine-dependent reaction to ionizing radiation, keratinocytes (HaCaT) without NIS were exposed in the same way. As indicators for the cellular reaction, the extent of DNA fragmentation was determined (Roche, Mannheim, Germany). Both cell types showed distinct ability for apoptosis as proven with camptothecin. The addition of "cold" iodine from 1 to 15 µg/ml without irradiation ("negative control") did not change the response in both cell types. Plausibly, the radio-sensitivity of both cell types did increase markedly with increasing radiation dose but the radiation effect is diminished if iodine is added to the thyroid cells beforehand. The DNA-damage in thyroid cells after addition of cold iodine is reduced by a factor of 2-3. The skin cells did not show an significant change of radio-sensitivity depending on the presence of cold iodine. Elementary iodine possibly acts as a radical scavenger and thus markedly reduces the secondary radiation damage caused by the formation of cytotoxic radicals. This intrinsic radioprotective effect of iodine is seen only in cells with NIS.

Retention efficacy and release of radioiodine in fume hoods.

Procedures to determine the release of hazardous gaseous substances including radioactive iodine are covered by different norms such as the European standard EN 14175 and the German national standard DIN 25466. The detection of sulphur hexafluoride (SF6) is required to comply with the prescribed methodology. The detection limit of this test is 4.5·10-7 mol/m3 in exhaust air. This detection limit would represent a very high activity in the region of 0.27 TBq/m3 leading to an unacceptable risk. We therefore developed a test using a filter system, consisting of a combination of filters capable of separating various chemical forms of airborne radioiodine. Air samples were collected directly in front of the fume hood and in the laboratory beside two different fume hoods of a similar construction with a final activated carbon filter for retention of radioiodine. Particular attention was therefore paid to air samples taken after passage over the filters. Significant differences in the degree of retention of iodine were found between the two fume hoods investigated. In one test a malfunction of the fume hood was demonstrated. In this case 0.148 × 10-3% of the total released activity per m3 air was found 1 cm in front of the hood sash. A remarkably high fraction of the activity released in the fume hood (1.3 × 10-3%/m3 air) was measured after the activated carbon filter. In the ambient air, values of up to 8.6 × 10-6% pro m3 laboratory air sampled were measured, despite a 6-8-fold air exchange. The selected procedure is a factor of 1011 (Schomäcker et al., 2001) more sensitive than the standard recommended methods (EN 14175). The standard test prescribed by the DIN/EN failed to reveal any inadequacy in the protective function of the radionuclide hood with respect to radioiodine retention.

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

BACKGROUND: Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. OBJECTIVE: To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). METHODS: 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. RESULTS: The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. CONCLUSIONS: In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Concordance in the interpretation of PET after chemotherapy in advanced stage Hodgkin lymphoma.

UNLABELLED: The aim was to analyze the degree of agreement between the central review panel and the local PET interpretation within the HD15 trial and its impact on subsequent treatment and progression free survival. PATIENTS, METHODS: The analysis set consisted of 739 patients with residues ≥ 2.5 cm after 6 or 8 cycles of BEACOPPesc from the HD15 trial performed by the German Hodgkin Study Group. The recommendation for or against further radiotherapy was based on the central [(18)F]FDG-PET interpretation. Central PET interpretation was compared to the local PET interpretation and concordance was measured using Cohen's Kappa coefficient. Prognostic impact of the analysis of concordance between local and central PET interpretations was evaluated using progression free survival (PFS); groups were compared with the log rank test. RESULTS: The central panel rated 548 of 739 patients (74%) as PET negative. Of these, 513 were also rated as PET negative in the local PET interpretation. PET positivity was seen by central reviewers in the remaining 191 patients (26%), in concordance with local reviewers in 155 cases. Even though substantial agreement was found (Cohen's Kappa 0.81), the interpretation of the central PET review panel led to a different therapeutic recommendation in 71/739 (10%) patients. PFS was equally high in groups in which the therapeutic regime had been changed on the basis of the central panel decision. CONCLUSION: High concordance is found between local and central reviewers with regard to PET interpretation in residual tissue after intense chemotherapy. The existence of the central PET review panel allows the identification of additional patients as PET negative so that radiotherapy can be safely omitted (35 of 548 patients = 4.7%).