Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study.

BACKGROUND: PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as 18F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. 18F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic 18F-FET PET and contrast-enhanced MRI in patients with HGG. METHODS: Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent 18F-GE-180 PET, dynamic 18F-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in 18F-GE-180 and 18F-FET PET. Dynamic 18F-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the Sørensen-Dice coefficient. RESULTS: The median TBRmax tended to be higher in 18F-GE-180 PET compared to 18F-FET PET [4.58 (2.33-8.95) vs 3.89 (1.56-7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in 18F-GE-180 PET compared to 18F-FET PET [5.45 (2.56-8.95) vs 4.06 (1.56-4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33-6.81) vs 3.79 (2.01-7.15) p = 1.000]. Only 5/20 cases showed higher TBRmax in 18F-FET PET compared to 18F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in 18F-GE-180 PET correlated with TTPmin (p > 0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4-236.0) ml] compared to BTVFET [19.3 (0.7-150.2) ml; p = 0.062] with a moderate spatial overlap [median Sørensen-Dice coefficient 0.55 (0.07-0.85)]. In MRI, median VOLCE [9.7 (0.1-72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p < 0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01-0.48)] and BTVFET [0.38 (0.01-0.68)]. CONCLUSION: PET with 18F-GE-180 and 18F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients' management.

Driving performance in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) present with impairments of their cognitive performance. It is still unknown whether cognitive deficits influence driving abilities in patients with COPD. The present study investigates driving performance in patients with COPD and healthy controls. Driving simulation was performed in 17 patients with COPD and 10 healthy controls. Patients with COPD demonstrated significantly worse results in terms of accident frequency in the simulated driving situation. No correlations existed between the severity of disease, assessed from the polysomnographical findings (e.g., lung function, blood gas analysis, sleep disturbance, nocturnal ventilation, and oxygen saturation), and driving performance. We conclude that impairments of driving performance in patients with COPD cannot be predicted on the basis of the severity of the disease. The impairment of driving performance in the simulated driving situation in COPD patients may have crucial consequences for driving licensing in these patients.

Systemic effects and side effects of interstitial techniques used in liver tissue.

BACKGROUND: Percutaneous ethanol injection (PEI) and cryosurgery are increasingly used for the treatment of liver malignancies. To create a safety margin and to destroy completely diffusely growing tumors, the precise destruction of healthy liver tissue is necessary. Little is known about the effects of operating on this type of tissue. This study evaluated the effects and side effects of PEI and cryosurgery when applied to normal parenchyma of the liver. STUDY DESIGN: Two groups of six minipigs each were treated with either PEI or cryosurgery to create necrosis in the liver. During and after the procedures, vital signs were monitored and necrotic areas were observed by ultrasonography. Standard and immunohistochemistry stains were made from samples of the necrosis, the liver, and the lung. RESULTS: In the PEI group, thromboembolic complications occurred in all animals (fatality rate 50%). Hematogenous spread of hepatocytes was demonstrated by immunohistochemistry and was a cause of pulmonary embolism. In the cryosurgery group, neither specific complications nor signs of cell spillage occurred. Because of an isolating effect of blood perfusion, hepatocytes close to the portal triads were less damaged, vital cells were present in the periphery, and the necroses were smaller than the induced lesions. CONCLUSIONS: The effect of PEI in healthy liver tissue is unpredictable. This makes the creation of a safety margin or the treatment of a diffusely infiltrating tumor impossible. PEI always introduces the risk of hematogenous cell spread. Effects of cryosurgery are less dependent on tissue qualities. In both techniques, the real extent of complete tissue destruction cannot be visualized by ultrasonography.

A disposable biosensor for urea determination in blood based on an ammonium-sensitive transducer.

A potentiometric urea-sensitive biosensor using a NH4(+)-sensitive disposable electrode in double matrix membrane (DMM) technology as transducer is described. The ion-sensitive polymer matrix membrane was formed in the presence of an additional electrochemical inert filter paper matrix to improve the reproducibility in sensor production. The electrodes were prepared from one-side silver-coated filter paper, which is encapsulated for insulation by a heat-sealing film. A defined volume of the NH4(+)-sensitive polymer matrix membrane cocktail was deposited on this filter paper. To obtain the urea-biosensor a layer of urease was cast onto the ion-sensitive membrane. Poly (carbamoylsulfonate) hydrogel, produced from a hydrophilic polyurethane prepolymer blocked with bisulfite, served as immobilisation material. The disposable urea sensitive electrode was combined with a disposable Ag/AgCl reference electrode to obtain the disposable urea biosensor. The sensor responded rapidly and in a stable manner to changes in urea concentrations between 7.2 x 10(-5) and 2.1 x 10(-2)mol/l. The detection limit was 2 x 10(-5) mol/l urea and the slope in the linear range 52 mV/decade. By taking into consideration the influence of the interfering K(+)- and Na(+)-ions the sensor can be used for the determination of urea in human blood and serum samples (diluted or undiluted). A good correlation was found with the data obtained by the spectrophotometric routine method.

Disposable sodium electrodes.

In this paper we describe a disposable sodium sensor in double matrix membrane technology. This sensor is prepared from filter paper with an evaporated silver conducting line on one side. For insulation the sensor is laminated with a pre-perforated heat-sealing film. A defined volume of an ion-sensitive polymer matrix membrane cocktail is filled into one hole. So an ion-sensitive coated film sensor in double matrix membrane technology is produced. The double matrix membrane is formed by the polymer matrix membrane and by the additional filter paper matrix. The response behaviour of the sodium electrode is comparable with conventional macro ion-selective electrodes. By this technology a mass production of low cost sensors is possible.

Circadian rhythms in Neurospora crassa: oligomycin-resistant mutations affect periodicity.

Nuclear mutations conferring resistance to oligomycin, a mitochondrial inhibitor, shorten the period of the circadian conidiation rhythm of Neurospora crassa from the normal 21.5 hours to 18 to 19 hours and slow the linear growth rate by 30 percent. These olir mutations map very close to frq, a locus at which mutations affecting periodicity have been previously obtained. The possibilities are discussed that mitochondria are involved in circadian rhythm generation and that certain period-length mutations affect mitochondrial functions.