(18F) barbiturates as structurally novel PET tracers with diagnostic potential in Alzheimer's diseaseCalamai, Elisa January 2014 (has links)
Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. Although the exact pathogenesis of AD remains unclear, accumulation of β- amyloid (Aβ) plaques seems to be among the causative events. In view of this, Aβ- PET imaging is considered to be a powerful non-invasive diagnostic tool that could also contribute to the development of therapies by monitoring responses. However, Aβ-PET ligands approved so far can only detect heavy plaque load and cannot replace post-mortem examination of brain tissue. The aim of this multidisciplinary study was to develop structurally novel PET tracers for AD. We focused on barbiturates for two main reasons: (i) barbiturates have an excellent ability to cross the blood-brain-barrier, (ii) they are chelators of cations involved in AD. A group of seven “cold” fluorinated barbiturates, along with the corresponding precursors for the “hot” radiosyntheses, was designed and synthesised. All the experimental logP values fell into the optimum range for brain uptake. Barbiturate 1a (Figure I) was selected for further investigations. Upon assessment of its affinity and specificity for Aβ, the radiosynthesis of [18F]1a was optimised. The imaging potential of this tracer was investigated in vivo in pre-clinical mouse models of AD. Brain PET/CT scans with [18F]1a showed reproducible brain uptake and clearance in three different mouse genotypes (WT, APP/PS1 and PLB2-Tau). The significantly higher uptake observed in APP/PS1 mice provided evidence for (i) the in vivo targeting of Aβ- plaques and (ii) the specificity of the tracer towards Aβ pathology. Finally, we designed a second-generation of barbiturates incorporating stilbene groups as dual metal/Ab targeting tracers and we developed a partial synthesis. With this study we paved the way for a larger scale research endeavour that may ultimately result in the rational design of an optimised lead tracer with the potential to ultimately translate into clinical use.
Fluoro-deoxy-carbohydrates as prosthetic groups for PET imaging : studies towards novel PET tracers for the cannabinoid system and angiogenesis-related receptorsFrau, Simona January 2015 (has links)
A novel class of potential positron emission tomography (PET) radiotracers for imaging aminopeptidase N (also known as APN or CD13) and cannabinoid type 1 (CB1) receptors were designed and synthesised with an efficient chemical strategy. Both targets have remarkable diagnostic and therapeutic potential, in fact the CD13 receptors are over-expressed during tumour angiogenesis and the CB1 receptors are highly expressed in the brain playing important functions in several pathophysiological processes. The target compounds were obtained by means of oxime-bio-conjugation between fluoro-deoxy-carbohydrates, used as prosthetic groups, and hydroxylamine-functionalised cyclic NGR (asparagine-glycine-arginine) motif sequences for CD13 receptor and rimonabant-type pyrazoles for the CB1 receptor. In particular, aminooxy-cyclic NGR peptides were conjugated with the novel prosthetic group 5-FDR (5-fluoro-5-deoxy-D-ribose) and the aminooxy- pyrazole-type cannabinoid molecules were conjugated with both 5-FDR and with FDG (2-fluoro-2-deoxy-D-glucose). 5-FDR proved to be superior to FDG, as the bioconjugation reaction occurred in milder conditions (room temperature vs 100 °C) and at faster rate. Furthermore, we observed that the rate of the oxime bond formation depends on the solubility of the aminooxy-functionalized core used. In fact, the bioconjugation with hydrophilic cyclic aminooxy-NGR peptides was faster than in the case of lipophilic aminooxy-pyrazoles (10 min vs 20-30 min). The receptor affinity is decreased in the case of the CB1 receptors after conjugation with the fluoro-carbohydrates. This is not observed with the conjugated NGR peptides, which maintain similar affinity for the CD13 receptor compared with the unconjugated NGR. In conclusion, we have developed an efficient strategy for the synthesis of a novel class of CD13 ligands, which may be also produced in radiofluorinated form, and explored a novel bioconjugation strategy for CB1 receptor ligands. Both may have important applications in the development of PET tracers.
No description available.
Lee, Ki Sung.
Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 113-124).
Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: oxygen consumption; PET; blood flow. Includes bibliographical references (p. 58-61).
18F FDG PET-CT scan in nasopharyngeal carcinoma and non-Hodgkin's lymphoma: two common cancers of the Hong KongpopulationChan, Kit-sum., 陳潔沁. January 2010 (has links)
published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy
Prevalence and factors associated with brown adipose tissue detected by 18F-FDG PET/CT in Hong Kong ChineseLeung, Tsz-mei., 梁紫微. January 2012 (has links)
Brown adipose tissue (BAT) is a unique organ in existence in mammals. It can induce non-shivering thermogenesis to control body temperature and energy balance through the expression of uncoupling protein 1 (UCP1). In our study, we aimed to evaluate the prevalence of BAT, as detected by fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography combined computer tomography (PET/CT), in a Hong Kong Chinese population. We also assessed the influence of age and sex to BAT in Hong Kong Chinese population. We also determined the factors associated with it, in particular, its relationship with overweight and other metabolic disorders such as diabetes mellitus. We analyzed 1765 consecutive 18F-FDG PET-CT scans of 1442 Chinese for the presence of BAT. Comparison of the variables between positive and negative BAT scans was performed using Student’s t-test. The association between maximum value of standardized uptake value (SUVmax) and variables were explored by Spearman correlation. The predictors of observed BAT were analyzed by multiple logistic regression to determine the significant predictors of positive BAT. The relationship between the monthly numbers of subjects with BAT and the respective mean monthly outdoor temperature was evaluated by Pearson’s correlation co-efficient. P < 0.05 was considered to be statistically significant. Brown adipose tissue was detected in 66 out of 1442 subjects (4.6%). BAT was significantly more commonly found in younger (43.7±13.5 years old vs. 61.4±14.2 years old, P<0.001) and female (59% vs. 46%, P<0.05) subjects. BAT also existed more frequently in subjects with lower body mass index (BMI) (21.2±3.1 kg/m2 vs. 22.4±3.7 kg/m2, P<0.01) and lower blood glucose level (5.9±0.9 mmol/L vs. 6.4±1.6 mmol/L, P<0.01). Also, BAT was detected only in subjects with no history of diabetes meallitus (DM) (0 vs. 10%, P<0.01). Moreover, lower outdoor temperature (21.6±4.6。C vs. 23.4±4.7。C, P<0.005) resulted in higher prevalence of detected BAT. In the multiple logistic regression test, age and mean monthly temperatures were the significant independent predictors of the presence of BAT (P< 0.001 and P=0.001). Age was also significantly correlated to SUVmax (P< 0.001). The monthly prevalence of positive BAT correlated negatively with mean monthly temperature by Pearson’s correlation (r = -0.79; P<0.01). To summarize, BAT was more commonly found in young, female subjects with lower BMI and blood glucose levels, and non-diabetes subjects. Age was the most important factor associated with the prevalence of BAT in humans. Lower outdoor temperature in winter can increase the prevalence of BAT even in Hong Kong’s sub-tropical climates. Also, there was an association of BAT with normal BMI (<=23) and lower blood sugar levels supporting the notion that BAT may potentially be a therapeutic target for obesity and diabetes. / published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy
Measurement of cerebrovascular perfusion reserve using single photon emission tomographic techniques王晴兒, Wong, Ching-yee, Oliver. January 1998 (has links)
published_or_final_version / Medicine / Master / Doctor of Medicine
Valenzano, Michael Peter
No description available.
Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (p. 143-157).
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