The potential use of cerium-doped lanthanum scintillators and optimisation of imaging processing in SPECT

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Ninth European Powder Diffraction Conference – Prague, September 2-5, 2004

Zeitschrift für Kristallographie. Supplement Volume 23 presents the complete Proceedings of all contributions to the IX European Powder Diffraction Conference in Prague 2004: Method Development and Application, Instrumental, Software Development, Materials Supplement Series of Zeitschrift für Kristallographie publishes Proceedings and Abstracts of international conferences on the interdisciplinary field of crystallography

Contrast Mechanisms & Wavefront Control in Coherent Nonlinear Microscopy

This Thesis deals with theoretical and experimental aspects of coherent nonlinear microscopy, with a special attention given to contrast mechanisms in Third Harmonic Generation (THG) microscopy.Ce travail de thèse présente une étude théorique et expérimentale de la microscopie non-linéaire cohérente pour l’étude de systèmes biologiques.Dans un premier temps, nous avons étudié l’origine des signaux et les mécanismes de contrastes en microscopie non-linéaire cohérente. En particulier, nous avons analysé l’influence de la microstructure de l’échantillon sur le signal de troisième harmonique rayonné. Nous illustrons cette discussion par une étude sur les contrastes endogènes de la cornée humaine. Dans un second temps, nous nous sommes intéressés à diverses méthodes de contrôle de front d’onde afin de moduler le contraste des images. Nous avons effectué par une étude théorique du signal obtenus à l’aide de modes d’excitation spatiale non-Gaussiens, puis avons implémenté deux systèmes de modulation du front d’onde : un modulateur acousto-optique permettant d’obtenir une profondeur de champ étendue en microscopie par fluorescence excitée à deux photons, et un miroir déformable permettant d’effectuer une correction dynamique des aberrations en microscope par génération de troisième harmonique. Enfin, nous nous sommes intéressés à l’application de la microscopie non-linéaire cohérente pour l’observation du développement précoce d’organismes modèles en embryologie: la drosophile et le poisson zèbre

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)