Visualization of fluoride ions in vivo using a gadolinium(III)-coumarin complex-based fluorescence/MRI dual-modal probe

A new Gadolinium(III)-coumarin complex, DO3A-Gd-CA, was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F-) in aqueous media and mice. DO3A-Gd-CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid (CA) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd-CA, the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity (r₁). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3σ/slope. The desirable features of the proposed DO3A-Gd-CA, such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd-CA could be potentially used in biomedical diagnosis fields

[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)

Evaluation of a Wobbling Method Applied to Correcting Defective Pixels of CZT Detectors in SPECT Imaging

In this paper, we propose a wobbling method to correct bad pixels in cadmium zinc telluride (CZT) detectors, using information of related images. We build up an automated device that realizes the wobbling correction for small animal Single Photon Emission Computed Tomography (SPECT) imaging. The wobbling correction method is applied to various constellations of defective pixels. The corrected images are compared with the results of conventional interpolation method, and the correction effectiveness is evaluated quantitatively using the factor of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). In summary, the proposed wobbling method, equipped with the automatic mechanical system, provides a better image quality for correcting defective pixels, which could be used for all pixelated detectors for molecular imaging

Evaluation of a Wobbling Method Applied to Correcting Defective Pixels of CZT Detectors in SPECT Imaging

In this paper, we propose a wobbling method to correct bad pixels in cadmium zinc telluride (CZT) detectors, using information of related images. We build up an automated device that realizes the wobbling correction for small animal Single Photon Emission Computed Tomography (SPECT) imaging. The wobbling correction method is applied to various constellations of defective pixels. The corrected images are compared with the results of conventional interpolation method, and the correction effectiveness is evaluated quantitatively using the factor of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). In summary, the proposed wobbling method, equipped with the automatic mechanical system, provides a better image quality for correcting defective pixels, which could be used for all pixelated detectors for molecular imaging