[en] This article deals with the regulation of the production and use of radiopharmaceuticals in Germany. As in other countries, radiopharmaceuticals may be used when licensed by the German equivalent of the Federal Drug Agency or in clinical trials. Furthermore, non-licensed radiopharmaceuticals can be administered to patients for diagnosis when they are produced in the same institution and not more than 20 doses per week and radiopharmaceutical are given. A prerequisite for these three ways of use is the production of the radiopharmaceutical in question according to the guidelines of the good manufacturing practice (GMP) which creates considerable problems for the usually small PET centers installed in the German university hospitals. German law offers a further possibility to apply non-licensed radiopharmaceuticals for clinical purposes: their administration to patients is not forbidden when performed by a physician who produces the substance himself or is at least responsible for its synthesis. This regulation has, however, been met with criticism by government agencies. (orig.)

No abstract available

[en] Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 μU/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of TSH. (orig.)

[en] Aim: disturbances of the D4 receptor subtype have been implicated in the genesis of a broad range of psychiatric disorders. In order to assess the suitability of a radioiodinated analogue of the D4-selective ligand FAUC 113 for tracer studies in vivo, we investigated the in-vivo stability, biodistribution and brain-uptake of 7-¹³¹I-FAUC 113 in Sprague-Dawley rats. Methods: radiolabelling was carried out with high radiochemical yield and specific activity. After intravenous injection, blood and tissue samples, taken of designated time intervals, were collected for analysis. Analyses of metabolites were performed by radio-hplc and radio-tlc. For in-vivo evaluation, sagittal cryo-sections of the rat brain were investigated by in-vitro and ex-vivo autoradiography on a μ-Imager system. Results: 7-¹³¹I-FAUC 113 was rapidly cleared from blood. Highest uptake was observed in kidney (0.603 ± 0.047% ID/g, n = 4) and liver (0.357 ± 0.070% ID/g, n = 4) at 10 min p.i.; 7-¹³¹I-FAUC 113 displayed rapid uptake (0.21-0.26% ID/g) and fast clearance in various brain regions consistent with the determined logP-value of 2.36±0.15 (n = 4). In-vivo stability of 7-¹³¹I-FAUC 113 was confirmed in the frontal cortex (> 95%). Ex-vivo autoradiography revealed a frontal cortex-to-cerebellum ratio of 1.57±0.13 at 10 min p.i. (n = 6). Coinjection with L-750667 could not suppress any putative specific binding of 7-¹³¹I-FAUC 113. In-vitro autoradiography using authentic 7-iodo-FAUC 113 or L-750667 failed to cause significant displacement of the radioligand. Conclusions: radioiodinated FAUC 113 does not allow imaging of D4 receptors in the rat brain in vivo nor in vitro. Further work should aim at the development of selective dopamine D4 radioligands with improved tracer characteristics, such as receptor affinity and subtype selectivity, specific activity or blood-brain-barrier permeability. (orig.)

[en] Aim: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of ¹⁸F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. Methods: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm². Results: In rat hippocampal slices, FDG accumulated with 1 300 000 ± 68 000 counts/mm², whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 ± 370 000 counts/mm². The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. Conclusions: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo. (orig.)

[en] 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. - Highlights: • The retention efficiency of fume hoods in which radioactivity is handled was tested. • The test prescribed by international standards uses chemical substances which are proven to be inadequate. • We propose an alternative method of testing fume hoods in laboratories where radionuclides are handled.