Probing Alzheimer's pathology: Exploring the next generation of FDDNP analogues for amyloid β detection.

Fluorescent probes are a powerful tool for imaging amyloid β (Aβ) plaques, the hallmark of Alzheimer's disease (AD). Herein, we report the synthesis and comprehensive characterization of 21 novel probes as well as their optical properties and binding affinities to Aβ fibrils. One of these dyes, 1Ae, exhibited several improvements over FDDNP, an established biomarker for Aβ- and Tau-aggregates.

Assessment of Regional Lung Ventilation with Positron Emission Tomography Using the Radiofluorinated Gas [F]SF: Application to an Animal Model of Impaired Ventilation.

Purpose: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [F]SF as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation.

Procedures: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group).

Longitudinal evaluation of neuroinflammation and oxidative stress in a mouse model of Alzheimer disease using positron emission tomography.

Background: Validation of new biomarkers of Alzheimer disease (AD) is crucial for the successful development and implementation of treatment strategies. Additional to traditional AT(N) biomarkers, neuroinflammation biomarkers, such as translocator protein (TSPO) and cystine/glutamine antiporter system (x), could be considered when assessing AD progression. Herein, we report the longitudinal investigation of [F]DPA-714 and [F]FSPG for their ability to detect TSPO and x biomarkers, respectively, in the 5xFAD mouse model for AD.

Evaluation of Multifunctional Gold Nanorods for Boron Neutron Capture and Photothermal Therapies.

The incidence and mortality of cancer demand more innovative approaches and combination therapies to increase treatment efficacy and decrease off-target side effects. We describe a boron-rich nanoparticle composite with potential applications in both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). Our strategy is based on gold nanorods (AuNRs) stabilized with polyethylene glycol and functionalized with the water-soluble complex cobalt (dicarbollide) ([3,3'-Co(1,2-CBH)]), commonly known as COSAN.

Comparison of analytical methods for antibody conjugates with application in nuclear imaging - Report from the trenches.

Introduction: Monoclonal antibodies (mAbs) are widely used in nuclear imaging. Radiolabelling with positron emitting radionuclides, typically radiometals, requires the incorporation of a bifunctional chelator for the formation of the radiometal-mAb complex. Additionally, mAbs can be conjugated with small molecules capable to undergo bioorthogonal click reactions in vivo, enabling pre-targeting strategies.

Swarming behavior and in vivo monitoring of enzymatic nanomotors within the bladder.

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo.

Longitudinal evaluation of a novel BChE PET tracer as an early biomarker in the brain of a mouse model for Alzheimer disease.

The increase in butyrylcholinesterase (BChE) activity in the brain of Alzheimer disease (AD) patients and animal models of AD position this enzyme as a potential biomarker of the disease. However, the information on the ability of BChE to serve as AD biomarker is contradicting, also due to scarce longitudinal studies of BChE activity abundance. Here, we report C-labeling, stability, biodistribution, and longitudinal study on BChE abundance in the brains of control and 5xFAD (AD model) animals, using a potent BChE selective inhibitor, [C], and positron emission tomography (PET) in combination with computerised tomography (CT).

Synthesis and Biochemical Evaluation of Warhead-Decorated Psoralens as (Immuno)Proteasome Inhibitors.

The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. Selective inhibition of its catalytic activities is therefore a viable approach for the treatment of these diseases.

Pre-targeting with ultra-small nanoparticles: boron carbon dots as drug candidates for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a promising cancer treatment exploiting the neutron capture capacity and subsequent fission reaction of boron-10. The emergence of nanotechnology has encouraged the development of nanocarriers capable of accumulating boron atoms preferentially in tumour cells. However, a long circulation time, required for high tumour accumulation, is usually accompanied by accumulation of the nanosystem in organs such as the liver and the spleen, which may cause off-target side effects.

Oral Treatment with Iododiflunisal Delays Hippocampal Amyloid-β Formation in a Transgenic Mouse Model of Alzheimer's Disease: A Longitudinal in vivo Molecular Imaging Study1.

Background: Transthyretin (TTR) is a tetrameric, amyloid-β (Aβ)-binding protein, which reduces Aβ toxicity. The TTR/Aβ interaction can be enhanced by a series of small molecules that stabilize its tetrameric form. Hence, TTR stabilizers might act as disease-modifying drugs in Alzheimer's disease.

Radiochemistry: A Useful Tool in the Ophthalmic Drug Discovery.

Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT) are ultra-sensitive, fully translational and minimally invasive nuclear imaging techniques capable of tracing the spatiotemporal distribution of positron (PET) or gamma (SPECT) emitter-labeled molecules after administration into a living organism. Besides their impact in the clinical diagnostic, PET and SPECT are playing an increasing role in the process of drug development, both during the evaluation of the pharmacokinetic properties of new chemical entities as well as in the proof of concept, proof of mechanism and proof of efficacy studies. However, they have been scarcely applied in the context of ophthalmic drugs.

Negishi coupling reactions with [C]CHI: a versatile method for efficient C-C bond formation.

Herein, we present a fast, efficient and general one-pot method for the synthesis of 11C-labelled compounds via the Negishi cross-coupling reaction. Our approach, based on the in situ formation of [11C]CH3ZnI and subsequent reaction with aryl halides or triflates, has proven efficient to synthesize [11C]thymidine, a biologically relevant compound with potential applications as a proliferation marker. Theoretical calculations have shown irreversible formation of a tetracoordinated nucleophilic 11C-Zn(ii) reagent and electronic requirements for an efficient Negishi coupling.

Design, Syntheses, and in Vitro Evaluation of New Fluorine-18 Radiolabeled Tau-Labeling Molecular Probes.

Deposition of aggregates of hyperphosphorylated tau protein is a hallmark of tauopathies like Alzheimer and many other neurodegenerative diseases. A sensitive and selective method of in vivo detection of tau-aggregate presence and distribution could provide the means of an early diagnosis of tau-associated diseases. Furthermore, the use of selective molecular probes that enable histochemical differentiation of protein aggregates post-mortem would be advantageous for the insight into the properties of tau protein aggregates.

Synthesis of Naphthalene-Based Push-Pull Molecules with a Heteroaromatic Electron Acceptor.

Naphthalene derivatives bearing electron-accepting and electron-donating groups at the 2,6-positions belong to the family of D-π-A push-pull dyes. It has been found that these compounds, e.g.