Quantitative PET-CT Perfusion Imaging of Prostate Cancer

Functional imaging of 18F-Fluorocholine PET holds promise in the detection of dominant prostatic lesions. Quantitative parameters from PET-CT Perfusion may be capable of measuring choline kinase activity, which could assist in identification of the dominant prostatic lesion for more accurate targeting of biopsies and radiation dose escalation. The objectives of this thesis are: 1) investigate the feasibility of using venous TACs in quantitative graphical analysis, and 2) develop and test a quantitative PET-CT Perfusion imaging technique that shows promise for identifying dominant prostatic lesions. Chapter 2 describes the effect of venous dispersion on distribution volume measurements with the Logan Plot. The dispersion of venous PET curves was simulated based on the arterio-venous transit time spectrum measured in a perfusion CT study of the human forearm. The analysis showed good agreement between distribution volume measurements produced by the arterial and venous TACs. Chapter 3 details the mathematical implementation of a linearized solution of the 3-Compartment kinetic model for hybrid PET-CT Perfusion imaging. A noise simulation determined the effect of incorporating CT perfusion parameters into the PET model on the accuracy and variability of measurements of the choline kinase activity. Results indicated that inclusion of CT perfusion parameters known a priori can significantly improve the accuracy and variability of imaging parameters measured with PET. Chapter 4 presents the implementation of PET-CT Perfusion imaging in a xenograft mouse model of human prostate cancer. Image-derived arterial TACs from the left ventricle were corrected for partial volume and spillover effects and validated by comparing to blood sampled curves. The PET-CT Perfusion imaging technique produced parametric maps of the choline kinase activity, k3. The results showed that the partial volume and spillover corrected arterial TACs agreed well with the blood sampled curves, and that k3max was significantly correlated with tumor volume, while SUV was not. In summary, this thesis establishes a solid foundation for future clinical research into 18F-fluorocholine PET imaging for the identification of dominant prostatic lesions. Quantitative PET-CT Perfusion imaging shows promise for assisting targeting of biopsy and radiation dose escalation of prostate cancer

Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats

Background—The plasma kallikrein-kinin (K-K) system is activated in acute and chronic relapsing intestinal inflammation induced in Lewis rats by intramural injection of exogenous bacterial components. Aims—To determine whether this effect is model specific, K-K system activation was investigated in a modified indomethacin induced enterocolitis model, as well as bradykinin 2 (B2) receptor distribution in the normal and acutely inflamed intestine. Methods—Lewis rats injected with daily sublethal doses of indomethacin for two days developed acute (two days) and chronic (14 days) intestinal inflammation. Plasma prekallikrein (amidolytic), high molecular weight kininogen (HK, coagulant) and cleavage of HK (western blot) were assayed to detect K-K activation. Results—Liver and spleen weights were significantly higher, and body weights and haematocrit values were significantly lower in the indomethacin group than in the control group. During both acute and chronic phases, rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels, and by HK cleavage. Plasma T kininogen (a major acute phase protein) was significantly elevated. B2 receptors were identified in both normal and inflammatory intestine with more prominent specific immunohistochemical staining in the acutely inflamed tissue. Conclusions—K-K system activation occurs in association with both acute and chronic phases of intestinal injury, regardless of the triggering agent, suggesting that activation of this system is integrally involved in intestinal inflammation in genetically susceptible hosts. Localisation of B2 receptors across intestinal layers provides a structural basis for the kinin function in the intestine

Behavioral Economics and the Public Sector

This thesis consists of four essays dealing with topics that are relevant for the public sector. The essays cover diverse issues of economics partly overlapping with political science. The topics reach from the taxation of labor over monetary policy to preferences over voting institutions. Throughout this thesis it is, in contrast to classical economics, not assumed that humans are necessarily fully rational. Once full rationality is no longer assumed, experiments become an important tool to learn about human behavior. Consequently, most of the work in this thesis makes use of economic experiments

Des-Arg9Bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: Role of serum ACE and aminopeptidase P

NRC publication: Ye