Thermodynamic, kinetic and NMR relaxometric studies of Mn(II) complexes as MRI probes

The main goal of this thesis is the characterization in aqueous solutions of new Mn(II) complexes as MRI probes. Our investigation included thermodynamic, kinetic and detailed 1H and 17O NMR relaxometric measurements. We have taken into account Mn-complexes belonging to two different main types of structural units. One encompasses the Mn(II) complexes containing the pentadentate coordinating units 6,6-((methylazanediyl)bis(methylene))dipicolinic acid. We considered several derivatives of the monomeric DPAMA ligand, including mono-, bi- and trinuclear bis-hydrated complexes (Chapter 4). In addition, we investigated a number of derivatives featuring different side arms and a couple of lipophilic derivatives (Chapter 5). All these complexes represent a fairly homogeneous series that has allowed us to obtain useful information on the relationship between the molecular structure, the thermodynamic stability and the relaxation parameters. The other class of complexes are those containing the macrocyclic unit cyclen and two coordinating pendant arms. These macrocyclic derivatives have been studied in detail, considering the chemical nature of the pendant arms, their relative position (cis/trans), the possible presence of isomers with different states of hydration, the kinetic and thermodynamic stability of the complexes and their relaxometric properties (Chapter 6). The synthesis of two novel derivatives bearing hydrophobic pendant groups enabled the investigation of the binding association with human serum albumin (Chapter 7). The global set of experimental results has allowed us to deepen our understanding of the chemistry of Mn(II) complexes as potential MRI probes. We are confident that the new information gained will help in the future design and development of more effective and safer MRI contrast enhancing agents

Limitations and pitfalls of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) scintigraphy

Tektrotyd kit was developed by Polatom company for 99mTc labeling to make an alternative tracer of somatostatin receptor scintigraphy available. Since 2005, 99mTc-EDDA/HYNIC-Tyr3-Octreotide has been used in clinical imaging and achieved high impact in management of patients with neuroendocrine tumors. Knowing the limitations and pitfalls is essential to provide ac­curate diagnosis. Therefore, the potential pitfalls associated with the use of 99mTc-EDDA/HYNIC-TOC are reviewed on the basis of own experience. Data were analyzed of 310 patients who underwent somatostatin receptor scintigraphy with 99mTc-Tektrotyd. Pitfalls during radiolabeling process or acquisition can worsen the sensitivity of SRS (somatostatin receptor scintigraphy). Recognizing physi­ological and clinical pitfalls, the diagnostic accuracy will improve

Thermodynamic stability, kinetic inertness and relaxometric properties of monoamide derivatives of lanthanide(III) DOTA complexes

A complete thermodynamic and kinetic solution study on lanthanide(III) complexes with monoacetamide (DOTAMA, L1) and monopropionamide (DOTAMAP, L2) derivatives of DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was undertaken with the aim to elucidate their stability and inertness in aqueous media. The stability constants of GdL1 and GdL2 are comparable, whereas a more marked difference is found in the kinetic inertness of the two complexes. The formation of the Eu(III) and Ce(III) complexes takes place via the formation of the protonated intermediates which can deprotonate and transform into the final complex through a OH-assisted pathway. GdL2 shows faster rates of acid catalysed decomplexation with respect to GdL1, which has a kinetic inertness comparable to GdDOTA. Nevertheless, GdL2 is one order of magnitude more inert than GdDO3A. A novel DOTAMAP-based bifunctional chelating ligand and its deoxycholic acid derivative (L5) were also synthesized. Since the coordinated water molecule in GdL2 is characterized by an exchange rate ca. two orders of magnitude greater than in GdL1, the relaxivity of the macromolecular derivatives of GdL5 should not be limited by the slow water exchange process. The relaxometric properties of the supramolecular adduct of GdL5 with human serum albumin (HSA) were investigated in aqueous solution by measuring the magnetic field dependence of the H-1 relaxivity which, at 20 MHz and 298 K, shows a 430% increase over that of the unbound GdL5 chelate. Thus, Gd(III) complexes with DOTAMAP macrocyclic ligands can represent good candidates for the development of stable and highly effective bioconjugate systems for molecular imaging applications

Agri-food business: Global challenges â Innovative solutions

The rise of a western-style middle class in many successful emerging economies like China currently is inducing deep structural changes on agricultural world markets and within the global agri-food business. As a result of both higher incomes and concerns over product safety and quality the global demand for high-quality and safe food products is increasing significantly. In order to meet the new required quality, globally minimum quality standards are rising and private standards emerging. All over the world these developments cause adjustments at the enterprise, chain and market levels. At the same time, the tremendously increasing demand for renewable energy has led to the emergence of a highly promising market for biomass production. This has far-reaching consequences for resource allocation in the agri-food business, for the environment, for the poor in developing countries and for agricultural policy reforms. The challenges increase with ongoing liberalisation, globalisation and standardisation, all of which change trade patterns for agricultural and food commodities, and influence production costs and commodity prices. The objective of the IAMO Forum is to show opportunities as well as risks for all participants of the food economy in the ongoing globalisation process: for small peasants in developing countries, farmers in Europe and globally active food enterprises and retailers. The success of enterprises depends on the ability to find innovative solutions with regard to the organisation of enterprises, chains, and markets, as well as future policy design. Concerning bio-energy strategies has to be identified to combat global warming most efficiently and concurrently attenuate the competition between "tank and table" on farmland. IAMO Forum 2008, as well as this book, would not have been possible without the engagement of many people and institutions. We thank the authors of the papers, as well as the referees. Furthermore we are highly indebted to MARLIES LOHR, NADINE GIEMSA and RONNY RECKE who in an outstanding way contributed to the organisation of the Forum. This is true as well for the IAMO administration, whose work we gratefully acknowledge. Many sponsors has funded the IAMO Forum 2008. We are very grateful to the German Research Foundation (DFG), The Federal Ministry of Food, Agriculture and Consumer Production in Germany, The Ministry of Cultural Affairs of the Federal State Saxony-Anhalt, Germany and last but not least the City of Halle. Further Conference sponsors are the BIONADE Corporation, Gaensefurther Mineral Water, The Wine Growers Association of the Region Saale-Unstrut, Germany, Obsthof am SüÃen See GmbH, Monsanto Company, KWS Saat AG, Sachsen-Anhalt-Tours, Baumkuchen Salzwedel and the Hallesches Brauhaus.Agribusiness, Agricultural and Food Policy, Agricultural Finance, Community/Rural/Urban Development, Industrial Organization, Institutional and Behavioral Economics, International Development, Marketing, Political Economy,

Arte e moda : algumas conexões possíveis

Orientação: Carla Beatriz Franco Ruschman

A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images.

Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25-30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians

A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images

<div><p>Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25–30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians.</p></div