Combined positron emission tomography/computed tomography (PET/CT) for imaging of orbital tumours and tumours extending into the orbit

Objective To assess clinical and radiological performance of combined positron emission tomography/computed tomography (PET/CT) in patients with secondary and primary intraorbital tumours. Methods 14 adults with secondary and 1 child with primary orbital masses underwent combined whole-body PET/CT. Radiopharmaceutical tracers applied were (18F)-fluorodeoxyglucose, (18F)-fluoroethylcholine (FEC) and (68Ga)-DOTATATE. Histopathology and/or all conventional radiographic work-up and clinical course served as standard of reference. Descriptive statistics and Fisher's exact test were used for analysis. Results PET/CT detected all orbital masses. All 15 patients had malignant disease. Local osseous infiltration was correctly identified in 11 patients. Lymph node metastases were present in two of eight patients (25%) with haematogenous orbital metastases and in five of six patients (83%) with infiltrative carcinoma (p=0.05). Further distant metastases were present in all eight patients suffering from orbital metastases, but only one patient with infiltrative carcinoma (17%) presented with disseminated disease (p=0.003). In one metastasis, PET/CT excluded vital orbital tumour tissue after radiation therapy. Local recurrence was detected in another patient suffering from prostate cancer. Conclusion PET/CT is a sensitive tool for the detection and localisation of orbital masses, enabling assessment of both morphology and cell metabolism. Detailed imaging of the head and neck region with a small field-of-view should be performed when suspecting lymphatic metastases. As metastatic disease to the orbit is associated with advanced disease, focus should be laid on whole-body imaging for staging of these patients. Different radiopharmaceutical tracers can be applied to distinguish the origin of orbital metastases

Inelastic quantum transport in superlattices: success and failure of the Boltzmann equation

Electrical transport in semiconductor superlattices is studied within a fully self-consistent quantum transport model based on nonequilibrium Green functions, including phonon and impurity scattering. We compute both the drift velocity-field relation and the momentum distribution function covering the whole field range from linear response to negative differential conductivity. The quantum results are compared with the respective results obtained from a Monte Carlo solution of the Boltzmann equation. Our analysis thus sets the limits of validity for the semiclassical theory in a nonlinear transport situation in the presence of inelastic scattering.Comment: final version with minor changes, to appear in Physical Review Letters, sceduled tentatively for July, 26 (1999

Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy

Background: Radiation-induced nephropathy is still dose limiting in radionuclide therapy of neuroendocrine tumors. We investigated the nephroprotective potential of the angiotensine converting enzyme inhibiting drug enalpril after [177Lu]-DOTATATE therapy in a murine model of radiation-induced nephropathy by renal scintigraphy. At first, the appropriate therapy activity to induce nephropathy was identified. Baseline scintigraphy (n = 12) entailed 12-min dynamic acquisitions after injection of 25 MBq [99mTc]-MAG3, which was followed by radionuclide therapy at four escalating activities of [177Lu]-DOTATATE: group (Gp) 1: 10 MBq;Gp 2: 20 MBq;Gp 3: 40 MBq;Gp 4: 65 MBq. Follow-up [99mTc]-MAG3 scintigraphy was carried out at days 9, 23, 44, and 65. The treatment activity for the intervention arm was selected on the basis of histological examination and declining renal function. In the second part, daily administration by gavage of 10 mg/kg/d enalapril or water (control group) was initiated on the day of radionuclide therapy. Follow-up scintigraphy was carried out at days 9, 23, 44, 65, and 86. We also created a non-therapy control group to detect therapy-independent changes of renal function over time. For all scintigraphies, mean renogram curves were analyzed and the "fractional uptake rate" (FUR;%I.D./min +/- SEM) of the tracer by the kidneys was calculated as an index of renal clearance. Results: At day 65 of follow-up, no significant change in the FUR relative to baseline (11.0 +/- 0.3) was evident in radionuclide therapy groups 1 (11.2 +/- 0.5) and 2 (10.1 +/- 0.6), but FUR was significantly reduced in groups 3 (8.93 +/- 0.6, p < 0.05) and 4 (6.0 +/- 0.8, p < 0.01);we chose 40 MBq [177Lu]-DOTATATE (Gp 3) for the intervention study. Here, at the last day of follow-up (day 86), FUR was unaltered in enalapril-treated mice (11.8 +/- 0.5) relative to the baseline group (12.4 +/- 0.3) and non-therapy group (11.9 +/- 0.8), whereas FUR in the control group had undergone a significant decline (9.3 +/- 0.5;p < 0.01). Histological examination revealed prevention of kidney damage by enalapril treatment. Conclusions: Treatment with enalapril is effective for nephroprotection during radionuclide therapy with [177Lu]-DOTATATE in mice. Although these results are only limitedly transferable to human studies, enalapril might serve as a promising drug in the mitigation of nephropathy following treatment with [177Lu]-DOTATATE

Evaluation of the Efficacy of a Combined Treatment Using the mTOR-Inhibitor Everolimus and [177Lu]Lu-DOTA-TATE in Nude CD1 Mice with SSTR-Expressing Pancreatic AR42J Xenograft Tumors

Therapy options for advanced pancreatic neuroendocrine tumors (pNETs) include the mTOR inhibitor everolimus and peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE, however further optimization in the therapeutic landscape is required as response rates are still low. In this study, we investigated the synergistic and potentially enhanced efficacy of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in a mouse model. Baseline [68Ga]Ga-DOTA-TATE PET scans were obtained five days after athymic CD1 mice were inoculated with AR42J tumor cells, before separating the animals into four groups. Group 1 received a placebo, group 2 everolimus, group 3 a placebo and PRRT, and group 4 everolimus and PRRT. The treatment response was monitored by manually measuring the tumor volumes (manual tumor volume, MTV) and conducting sequential [68Ga]Ga-DOTA-TATE PET scans at one, two, and four weeks after treatment induction. The biological tumor volume (BTV) was derived from PET scans using threshold-based volume of interest (VOI) measurements. Tracer uptake was measured semi-quantitatively as a tumor to background ratio (TBR). Mice were euthanized due to excessive tumor growth according to the ethics protocol;blood samples were drawn for the preparation of full blood counts and kidneys were obtained for histological analysis. For the histological assessment, a standardized score (renal damage score, RDS) was used. Full blood counts showed significantly increased numbers of neutrophils and lymphocytes in the groups receiving PRRT. All other parameters did not differ relevantly. In the histological analysis, groups receiving PRRT had a significantly higher RDS, whereas everolimus only tended to cause an increase in the RDS. Mice in groups 1 and 2 had to be euthanized due to excessive tumor growth two weeks after the start of the therapy, whereas follow-up in groups 3 and 4 comprised four weeks. PRRT significantly inhibited tumor growth;the administration of everolimus did not induce an additional effect. A good correlation existed between MTV and BTV. PRRT significantly reduced the TBR. [68Ga]Ga-DOTA-TATE PET is suitable for monitoring tumor growth in the applied model. The high efficacy of [177Lu]Lu-DOTA-TATE is not enhanced by the combination with everolimus

Multi-wavelength analysis of high energy electrons in solar flares: a case study of August 20, 2002 flare

A multi-wavelength spatial and temporal analysis of solar high energy electrons is conducted using the August 20, 2002 flare of an unusually flat (gamma=1.8) hard X-ray spectrum. The flare is studied using RHESSI, Halpha, radio, TRACE, and MDI observations with advanced methods and techniques never previously applied in the solar flare context. A new method to account for X-ray Compton backscattering in the photosphere (photospheric albedo) has been used to deduce the primary X-ray flare spectra. The mean electron flux distribution has been analysed using both forward fitting and model independent inversion methods of spectral analysis. We show that the contribution of the photospheric albedo to the photon spectrum modifies the calculated mean electron flux distribution, mainly at energies below 100 keV. The positions of the Halpha emission and hard X-ray sources with respect to the current-free extrapolation of the MDI photospheric magnetic field and the characteristics of the radio emission provide evidence of the closed geometry of the magnetic field structure and the flare process in low altitude magnetic loops. In agreement with the predictions of some solar flare models, the hard X-ray sources are located on the external edges of the Halpha emission and show chromospheric plasma heated by the non-thermal electrons. The fast changes of Halpha intensities are located not only inside the hard X-ray sources, as expected if they are the signatures of the chromospheric response to the electron bombardment, but also away from them.Comment: 26 pages, 9 figures, accepted to Solar Physic

Inter-Edge interaction in the Quantum Hall Effect

We consider effects of the interaction between electrons drifting along the opposite sides of a narrow sample under the conditions of the quantum Hall effect. A spatial variation of this interaction leads to backward scattering of collective excitations propagating along the edges. Experiments on propagation of the edge modes in samples with constrictions may give information about the strength of the inter-edge electron interaction in the quantum Hall regime.Comment: 12 Pages, Latex, Accepted for publication in PRL

Statistics of Raman-Active Excitations via Masurement of Stokes-Anti-Stokes Correlations

A general fundamental relation connecting the correlation of Stokes and anti-Stokes modes to the quantum statistical behavior of vibration and pump modes in Raman-active materials is derived. We show that under certain conditions this relation can be used to determine the equilibrium number variance of phonons.Time and temperature ranges for which such conditions can be satisfied are studied and found to be available in todays' experimental standards. Furthermore, we examine the results in the presence of multi-mode pump as well as for the coupling of pump to the many vibration modes and discuss their validity in these cases.Comment: 12 pages, 1 figure, accepted for publication in Phys.Rev.

Treatment with Octreotide in Patients with Well-Differentiated Neuroendocrine Tumors of the Ileum: Prognostic Stratification with Ga-68-DOTA-TATE Positron Emission Tomography

We investigated the use of Ga-68-DOTA-Tyr(3)-octreotate (Ga-68-DOTA-TATE) positron emission tomography (PET) and standardized uptake values (SUVs) to predict the effectiveness of treatment with the somatostatin analogue octreotide acetate (Sandostatin LAR) in patients with neuroendocrine tumors (NETs). Thirty patients with well-differentiated NETs of the ileum (grades G1 and G2) were studied with Ga-68-DOTA-TATE. The average SUV of a 50% isocontour volume of interest covering the lesion with maximum uptake (SUVmean) and the maximum SUV (SUVmax) were determined. Patients were followed up, and the time to progression was recorded. Twenty-one patients showed progressive disease at the end of the study;nine patients had stable disease. The median progression-free survival (PFS) was 51.0 weeks (95% confidence interval [CI] 26.4-75.6). A cutoff for the SUVmax of 29.4 and for the SUVmean of 20.3 could separate between patients with a long PFS (69.0 weeks; 95% CI 9.8-128.2) and a short PFS (26.0 weeks; 95% CI 8.7-43.3) response to octreotide acetate therapy. Patients with high radiotracer uptake had significantly higher PFS with a 2.9-fold higher chance for stable disease after 45 weeks;however, the prognostic performance of SUVmax on an individual basis was poor, with a sensitivity of 75% and a specificity of 64%. SUVmax and SUVmean of NET tumor lesions in Ga-68-DOTA-TATE PET are important prognostic indices for predicting the response to therapy with octreotide acetate

Comment on the letter of the Society of Vertebrate Paleontology (SVP) dated April 21, 2020 regarding “Fossils from conflict zones and reproducibility of fossil‑based scientific data”: Myanmar amber

Non peer reviewe

Study of Tau-pair Production in Photon-Photon Collisions at LEP and Limits on the Anomalous Electromagnetic Moments of the Tau Lepton

Tau-pair production in the process e+e- -> e+e-tau+tau- was studied using data collected by the DELPHI experiment at LEP2 during the years 1997 - 2000. The corresponding integrated luminosity is 650 pb^{-1}. The values of the cross-section obtained are found to be in agreement with QED predictions. Limits on the anomalous magnetic and electric dipole moments of the tau lepton are deduced.Comment: 20 pages, 9 figures, Accepted by Eur. Phys. J.