Assessment of a 6-arylaminobenzamide lead derivative as a potential core scaffold for S1P positron emission tomography radiotracer development.

Sphingosine-1-phosphate-5 receptors (S1P) are predominantly expressed in oligodendrocytes and as a result have been proposed as an important target in Multiple Sclerosis (MS). Selective S1P radiotracers could enable in vivo positron emission tomography (PET) imaging of oligodendrocytes activity. Here we report the synthesis, radiolabelling and first preclinical evaluation of the pharmacokinetics and binding properties of a lead 6-arylaminobenzamide derivative, 6-(mesitylamino)-2-methoxy-3-methylbenzamide (also named as TEFM180), as a potential core scaffold for development of novel S1P PET radiotracers.

Musketeer: a software tool for the analysis of titration data.

Musketeer is a powerful open-source software tool for the analysis of titration data, featuring a simple cross-platform graphical interface for importing data directly from UV-vis, fluorescence and NMR spectrometers, or from spreadsheets. The fast data analysis algorithm can be used to obtain equilibrium constants for simple binding isotherms, as well as for more complicated systems with multiple competing equilibria. Applications of Musketeer for the analysis of a range of different supramolecular and biomolecular systems are illustrated, including titrations with multiple spectroscopically active species, competitive binding assays, denaturation experiments, optimisation of concentrations as variables.

Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system.

Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26) that integrates reporters for complementary imaging modalities, flfluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression.

Selective Duplex Formation in Mixed Sequence Libraries of Synthetic Polymers.

Recognition-encoded melamine oligomers (REMO) are synthetic polymers that feature an alternating 1,3,5-triazine-piperazine backbone and side-chains equipped with either a phenol or phosphine oxide recognition unit. An automated method for the solid-phase synthesis (SPS) of REMO of any specified sequence has been developed starting from dichlorotriazine monomer building blocks. Complementary homo-oligomers with either six phenols or six phosphine oxides were synthesized and shown to form a stable duplex in nonpolar solvents by NMR denaturation experiments.

Noninvasive Stratification of Colon Cancer by Multiplex PET Imaging.

Purpose: The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression-based subtyping remain unknown.