1,721,567 research outputs found
Synthesis of 18F-Labelled β-Lactams by Using the Kinugasa Reaction
No full text© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PSMA - Targeted Clinical Molecular Imaging of Atherosclerosis:Correlation with Cardiovascular Risk Factors
No full textAim The early diagnosis of atherosclerotic changes to prevent ischemic events represents a clinical challenge. Prostate-specific membrane antigen (PSMA) as an established diagnostic in the field of prostate cancer also appears to detect neovascularization and inflammation in other diseases. We hypothesized that it might be also suited for detection of inflammation in atherosclerosis. Methods We analyzed data of 78 prostate cancer patients who received a PSMA ligand PET/CT for re-staging. The cardiovascular risk factors (CVRF) of each patient were documented. Target-to-background-ratios (TBR) were calculated from the individual uptake values for three different sections of thoracic aorta [ascending (AA) and descending aorta (AD), aortic arch (AoAC)]. Statistical analyses included a linear regression analysis with the PSMA ligand uptake values of the different arterial segments versus different CVRF as independent variables. Results The meanTBRmax was measured highest in the AoAC (1.66 +/- 0.33) compared to both other vessel sections (AA: 1.46 +/- 0.21, p=0.001; AD: 1.59 +/- 0.41, p=0.371). There was a correlation between the PSMA ligand uptake in all measured segments of the aorta and BMI, but only a significant correlation in the ascending aorta (r=0.347, p=0.001). This was confirmed in a subgroup analysis, which showed significantly higher uptake values in preadiposity (BMI >25) and obesity (BMI >30) patients in the ascending aorta (p=0.048). Conclusion PSMA ligand uptake in the ascending aorta was linked to BMI. PET detection of vascular PSMA ligand uptake may be indicative of vessel wall inflammation to some extent. However, PSMA ligands appear to be less suitable than other tracers for this purpose, given their absent correlation with most established CVRFs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Special Issue : Emerging Technologies for Medical Imaging Diagnostics, Monitoring and Therapy of Cancers
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Endogenous radiotherapy of triple negative breast cancer: the prostate-specific membrane antigen as a vascular target
No full textAims: The especially aggressive triple negative breast cancer (TNBC) lacks efficient therapeutic options, the patient prognosis is poor and the recurrence rates are high. Several angiogenesis inhibitors like bevacizumab only demonstrated limited therapeutic efficacy in the management of TNBC. Considering the vascular prostate-specific antigen (PSMA) expression in a variety of solid tumors including TNBC, the aim of this thesis was the evaluation of cellular PSMA expression patterns in the tumor and tumor-associated endothelial cells and the effect of [177Lu]Lu-PSMA-I&T on cell viability. Finally, the potential of [177Lu]Lu-PSMA-I&T should be evaluated in a therapeutic setting. Materials and methods: Chapter I provides a general introduction. Chapter II evaluates the current status quo of the development of radiolabeled ligands for imaging and treatment of breast cancer with a focus on the tumor microenvironment (TME). The in vitro investigation in Chapter III analyzed the PSMA expression in a panel of TNBC cell lines and breast cancer stem cells (BCSCs) and their endothelial co-culture. The conclusive in vivo study in Chapter IV evaluated the therapeutic efficacy of a full and a fractionated dose of [177Lu]Lu-PSMA-I&T in orthotopically xenografted mice. Results and discussion: The presence of TNBC cells induced PSMA expression and a morphological change in endothelial cells. Further, the BCSCs obviously harbour a high amount of PSMA splice variants which could be associated with invasion and therapy resistance. The application of [177Lu]Lu-PSMA-I&T had a stronger effect on the viability of the co-cultured endothelial cells than the tumor cells itself. Finally, the animal experiments provided in vivo evidence for the efficacy of [177Lu]Lu-PSMA-I&T in TNBC, where the full dose approach tended to a slightly higher efficacy regarding tumor growth inhibition and increased survival compared to the fractionated approach. The treatment was tolerated very well and no cytotoxic off-target effects were observed. Conclusion: The results of this thesis provide a strong rationale for the use of [177Lu]Lu-PSMA-I&T in the management of TNBC. As the therapeutic options are limited, patient prognosis and overall life quality could improve greatly with an effective treatment
Study Parameter impact in quantitative 90-Yttrium PET imaging for radioembolization treatment monitoring and dosimetry
No full textModulating resting state functional connectivity of the dorsolateral prefrontal cortex using transcranial magnetic stimulation and transcranial direct current stimulation
No full textSodium []Fluoride positron emission tomography for non-invasive identification of micro-calcifications as marker of atherosclerotic plaque vulnerability
No full textAims: Despite recent medical advances, cardiovascular disease remains the leading cause of death worldwide. Given the high sensitivity and specificity of Na[18F]F and [68Ga]Ga-Pentixafor for cardiovascular calcifications and inflammation respectively and positive emerging data of vitamin K on vascular health, the aim of this thesis was to assess the ability of both tracers to monitor disease progression and therapy with vitamin K.Materials and methods: Chapter I provided a general introduction. Chapter II identified Na[18F]F PET as the most suitable technique for detecting micro-calcification, after a structured PubMed search. Presenting the pros and cons of available treatments, vitamin K supplementation emerged as a possible safe and cost-effective option to inhibit vascular (micro)-calcification. In Chapter III, a unitary atherosclerotic mouse trial was designed to assess the ability of Na[18F]F PET/CT to monitor therapy and disease progression and of vitamin K to inhibit vascular calcification. In Chapter IV, a prospective double-blind placebo-controlled feasibility study was created to investigate the practicability of the results from the animal study in the human situation, using a hybrid PET/MRI. In Chapter V, the feasibility of monitoring plaque inflammatory status using [68Ga]Ga-Pentixafor was preclinically assessed.Results and discussion: After selecting Na[18F]F PET as a mean to image vascular (micro-)calcifications and Vitamin K to treat it, the preclinical trial was started. Here mice treated with Warfarin (i.e., a Vitamin K inhibitor) presented spotty calcifications on the CT in the proximal aorta. All the spots corresponded to dense mineralisations on the von Kossa staining. Mice with an advanced atherosclerosis did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. After the control, the Vitamin K treated animals had the lowest Na[18F]F uptake, suggestion its protective role. The results of the preclinical study will be tested in the INTRICATE clinical trial, where the primary endpoint is the temporal change of Na[18F]F uptake in human carotid artery atherosclerosis of the treatment arm (i.e., with vitamin K) and the placebo arm. [68Ga]Ga-Pentixafor seems to be able to correctly detect inflammatory changes in the atherosclerotic plaque morphology.Conclusion: This thesis argues for the practicability of Na[18F]F and [68Ga]Ga-Pentixafor PET to monitor atherosclerotic plaque progression and treatment, while serving as an argument for the increase in the recommended daily dose of vitamin K
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