Peptide Receptor Radionuclide Therapy with 177Lu-octreotate: clinical aspects

Somatostatin is a neuropeptide with a variety of functions and is produced in several tissues. The isoform somatostatin-14 (SS-14) is more biologically active than SS-28. Its main physiological function is to inhibit secretion of hormones such as growth hormone or thyroid stimulating hormone in the pituitary, insulin or glucagon in the pancreas and of exocrine gut secretion. The effects of somatostatin are mediated by binding to the somatostatin receptor (sst), which are G-protein-coupled receptors. Five sst subtypes have been identified (sst1 - sst5) which all have different roles. The naturally occurring SS-14 and SS-28 have high affinity for all these subtypes. Several tumours (Table 1), amongst others gastroenteropancreatic tumours (GEPNET), have overexpression of sst on the cell surface. This makes sst a possible target for therapy with somatostatin analogues to try and inhibit the secretion of bioactive substances by these tumours and possibly to slow down tumour growth. However, the biological half-life of SS-14 and SS-28 is short, and this makes it impossible to use them for therapeutic goals. With the invention of the cyclic octapeptide octreotide, half-life increased significantly and octreotide then could be used in treatment of patients with sst-positive tumours

Fundamental limits of NO formation in fuel-rich premixed methane-air flames

Increasingly stringent regulations on pollutant emission are the driving force for designers of natural-gas-fired combustion systems to find ways of controlling NOx formation. To achieve significant emissions reduction, more insight is needed into the mechanisms of NO formation. Martijn van Essen’s thesis provides insight into the effects of two NOx control strategies, flue-gas recirculation (FGR) and burner stabilization, on NO formation. Since many combustion systems operate under fuel-rich (oxygen deficient) conditions, the focus of the thesis was on fuel-rich premixed methane-air flames. The experiments were performed at reduced pressures, to facilitate the measurements of the distributions of temperature and concentrations of key species (CH, OH and NO) using the optical technique laser-induced fluorescence (LIF). Towards this end, a low-pressure flame cell was constructed, and protocols for quantifying the LIF measurements were implemented. The experimental results were compared with detailed calculations based on a chemical mechanism widely used in combustion. The experimental results demonstrate that both burner stabilization and FGR are promising techniques for lowering NO emissions in fuel-rich flames. A comparison with detailed calculations allowed tracing the mechanistic origins of the observed reduction in NO formation rate. However, due to the existence of multiple formation mechanisms, more research is needed in order to improve predictive power of the flame models, particularly under very rich conditions. The quantitative results in this thesis are ideally suited for improving these model

The Effect of Humidity on the Knock Behavior in a Medium BMEP Lean-Burn High-Speed Gas Engine

The effects of air humidity on the knock characteristics of fuels are investigated in a lean-burn, high-speed medium BMEP engine fueled with a CH4 + 4.7 mole% C3H8 gas mixture. Experiments are carried out with humidity ratios ranging from 4.3 to 11 g H2O/kg dry air. The measured pressure profiles at non-knocking conditions are compared with calculated pressure profiles using a model that predicts the time-dependent in-cylinder conditions (P, T) in the test engine (“combustion phasing”). This model was extended to include the effects of humidity. The results show that the extended model accurately computes the in-cylinder pressure history when varying the water fraction in air. Increasing the water vapor content in air decreases the peak pressure and temperature significantly, which increases the measured Knock Limited Spark Timing (KLST); at 4.3 g H2O/kg dry air the KLST is 19 °CA BTDC while at 11 g H2O/kg dry air the KLST is 21 °CA BTDC for the same fuel. Excellent agreement is observed between the calculated knock resistance (using the Propane Knock Index, PKI) and the measured knock resistance (KLST) for the range in water content in air studied in this work. Since the effect of water on autoignition delay time is negligible, the observed increase in knock resistance of the fuel-air mixture is due a decrease in pressure and temperature of the end gas with increasing water content in as a result of changes in the mass burning rate, and thermophysical properties of the fuel-air mixture

Experimental and Modeling Investigation of the Effectof H2S Addition to Methane on the Ignition and Oxidation at High Pressures

The autoignition and oxidation behavior of CH₄/H₂S mixtures has been studied experimentally in a rapid compression machine (RCM) and a high-pressure flow reactor. The RCM measurements show that the addition of 1% H₂S to methane reduces the autoignition delay time by a factor of 2 at pressures ranging from 30 to 80 bar and temperatures from 930 to 1050 K. The flow reactor experiments performed at 50 bar show that, for stoichiometric conditions, a large fraction of H₂S is already consumed at 600 K, while temperatures above 750 K are needed to oxidize 10% methane. A detailed chemical kinetic model has been established, describing the oxidation of CH₄ and H₂S as well as the formation and consumption of organosulfuric species. Computations with the model show good agreement with the ignition measurements, provided that reactions of H₂S and SH with peroxides (HO₂ and CH₃OO) are constrained. A comparison of the flow reactor data to modeling predictions shows satisfactory agreement under stoichiometric conditions, while at very reducing conditions, the model underestimates the consumption of both H₂S and CH₄. Similar to the RCM experiments, the presence of H₂S is predicted to promote oxidation of methane. Analysis of the calculations indicates a significant interaction between the oxidation chemistry of H₂S and CH₄, but this chemistry is not well understood at present. More work is desirable on the reactions of H₂S and SH with peroxides (HO₂ and CH₃OO) and the formation and consumption of organosulfuric compounds

Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

Introduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate). Materials and methods: All177Lu- octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included fo