Myelin-targeted, texaphyrin-based multimodal imaging agent for magnetic resonance and optical imaging.

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to GdIII . These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.

Inhibitory Activity Of Curcumin Derivatives Towards Metal-free And Metal-induced Amyloid-ß Aggregation.

When Alzheimer's disease (AD) progresses, several pathological features arise including accumulation of misfolded protein aggregates [e.g., amyloid-ß (Aß) plaques], metal ion dyshomeostasis, and oxidative stress. These characteristics are recently suggested to be interconnected through a potential factor, metal-associated Aß (metal-Aß) species. The role of metal-Aß species in AD pathogenesis remains unclear, however. To elucidate the contribution of metal-Aß species to AD pathology, as well as to develop small molecules as chemical tools and/or theranostic (therapeutic and diagnostic) agents for this disease, curcumin (Cur), a natural product from turmeric, and its derivatives have been studied towards both metal-free and metal-induced Aß aggregation. Although Cur has indicated anti-amyloidogenic activities and antioxidant properties, its biological use has been hindered due to low solubility and stability in physiologically relevant conditions. Herein, we report the reactivity of Cur and its derivatives (Gd-Cur, a potential multimodal Aß imaging agent; Cur-S, a water soluble derivative of Cur that has substitution at the phenolic hydroxyls) with metal-free Aß and metal-Aß species. Our results and observations indicate that Gd-Cur could modulate Cu(II)-triggered Aß aggregation more noticeably over metal-free or Zn(II)-induced analogues; however, Cur-S was not observed to noticeably modulate Aß aggregation with and without metal ions. Overall, our studies present information that could aid in optimizing the molecular scaffold of Cur for the development of chemical tools or theranostics for metal-Aß species.

A multimodal, ß-amyloid-targeted contrast agent.

A multimodal, ß-amyloid-targeted contrast agent was synthesized and studied in vitro. The agent has a higher relaxivity than a clinically approved contrast agent and interacts with ß-amyloid aggregates producing changes in relaxation rate and fluorescence emission.

Strategies for Target-Specific Contrast Agents for Magnetic Resonance Imaging.

This review describes recent research efforts focused on increasing the specificity of contrast agents for proton magnetic resonance imaging (MRI). Contrast agents play an indispensable role in MRI by enhancing the inherent contrast of images; however, the non-specific nature of current clinical contrast agents limits their usefulness. This limitation can be addressed by conjugating contrast agents or contrast-agent-loaded carriers-including polymers, nanoparticles, dendrimers, and liposomes-to molecules that bind to biological sites of interest. An alternative approach to conjugation is synthetically mimicking biological structures with metal complexes that are also contrast agents. In this review, we describe the advantages and limitations of these two targeting strategies with respect to translation from in vitro to in vivo imaging while focusing on advances from the last ten years.

Preparation, purification, and characterization of lanthanide complexes for use as contrast agents for magnetic resonance imaging.

Polyaminopolycarboxylate-based ligands are commonly used to chelate lanthanide ions, and the resulting complexes are useful as contrast agents for magnetic resonance imaging (MRI). Many commercially available ligands are especially useful because they contain functional groups that allow for fast, high-purity, and high-yielding conjugation to macromolecules and biomolecules via amine-reactive activated esters and isothiocyanate groups or thiol-reactive maleimides. While metalation of these ligands is considered common knowledge in the field of bioconjugation chemistry, subtle differences in metalation procedures must be taken into account when selecting metal starting materials. Furthermore, multiple options for purification and characterization exist, and selection of the most effective procedure partially depends on the selection of starting materials. These subtle differences are often neglected in published protocols. Here, our goal is to demonstrate common methods for metalation, purification, and characterization of lanthanide complexes that can be used as contrast agents for MRI (Figure 1). We expect that this publication will enable biomedical scientists to incorporate lanthanide complexation reactions into their repertoire of commonly used reactions by easing the selection of starting materials and purification methods.