Typologie d'actualités: Team Chemistry, Imaging and Exobiology

Towards new imaging markers for in vivo detection of pathologies such as Alzheimer’s or diabetes

The accumulation of aggregates of certain non-soluble peptides in tissues is characteristic of several pathologies, such as Alzheimer's and Parkinson's diseases, or diabetes. The detection of these amyloid deposits by in vivo imaging would be very useful for an early diagnostic and a better understanding of the molecular mechanisms of these diseases. Researchers from the Molecular Biophysics Center (CBM) and the Toulouse Coordination Chemistry Laboratory (LCC), in collaboration with Portuguese and Hungarian scientists, have taken an important step forward in the design of imaging agents that specifically recognize these amyloid deposits. This work is on the cover of Chemistry A European Journal.

Read more on the website of CNRS Chemistry Institute (INC)




Detection of amyloid peptides: biomarkers for Alzheimer’s Disease and Diabetes

Metal chelates targeted to amyloid peptides are widely explored as diagnostic tools or therapeutic agents for amyloidogenic diseases. For example, gadolinium complexes can be used as MRI probes, while radiocomplexes (64Cu, 99mTc, etc) can be exploited for nuclear imaging. Other metal complexes capable of preventing aggregate formation are proposed to derive therapeutic strategies.

All these molecules are amphiphilic, composed of a hydrophilic part (containing the metal) and a hydrophobic one (capable of targeting the amyloid aggregates). This particular structure enables the formation of micelles in solution.

The groups of CBM and LCC (Toulouse) have found that this micellisation property has drastic and unexpected consequences on their ability to recognize amyloid peptides and a high impact on their in vivo biodistribution.

The researchers have developed a novel probe with nanomolar affinity towards Aβ and amylin, biomarkers of Alzheimer’s Disease and Ddiabetes, respectively.

This exceptional affinity for a metal complex is only obtained if the complex is present as “single molecule”. Once in the micellar form, this affinity drops by 1000-fold.

These results have a direct consequence for the design of novel imaging and therapeutic probes for amyloidogenic pathologies.

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Pure and stable white light

Current white light sources, such as LEDs, tend to oscillate between different color variations, which distorts the perception of the human eye. This limitation can be very disabling, even dangerous, during surgery or in the work of graphic designers and artists.

Researchers from the Center for Molecular Biophysics and the University of Michigan (United States) have developed a new system, based on dysprosium atoms and metallacrowns, which gives exactly white light that does not vary with conditions wear or temperature.

This work has been published in the Journal of the American Chemical Society.

See the information on the CNRS Institute of Chemistry website.

Unveiling billion-year old life forms with X-ray vision

An international team of scientists from Brazil, France and Switzerland with financial support from the Serrapilheira Institute and Fapesp, has obtained the most detailed 3D views ever achieved of very ancient traces of life on Earth. The studied microfossils, from the Gunflint Formation, in Canada, are approximately 1.9 billion years old, and are the preserved remains of microorganisms similar to bacteria existing today, but from a period when only microscopic life existed on Earth. Using an advanced imaging method based on synchrotron light, unprecedented details of the shape, composition and preservation of these microfossils was attained. Moreover, in one locality, fossils previously termed “hematite-coated” are revealed to be composed of organic material – invisible in optical microscopy – coated with crystals of the iron oxide maghemite, instead of hematite. This finding challenges our understanding of past life and opens exciting perspectives for the study of even older fossils or future samples returned from Mars.

Maldanis, L., Hickman-Lewis, K., Verezhak, M. et al. Nanoscale 3D quantitative imaging of 1.88 Ga Gunflint microfossils reveals novel insights into taphonomic and biogenic characters. Scientific Reports 10, 8163 (2020). https://doi.org/10.1038/s41598-020-65176-w

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3D observation of microfossils

Organometallic networks for the near-infrared emission of lanthanides

Researchers from the group "Luminescent lanthanide compounds, spectroscopy and optical bioimaging" and the University of Pittsburgh (USA) have designed a rigid three-dimensional chemical system of organometallic network type composed of lanthanides and organic molecules. A major originality of this work is based on the use of the cavity of this network to generate in situ the molecular system sensitizing the lanthanide cations. This new approach has the advantage, among other things, of allowing the excitation length to be controlled. This network is well suited to the real conditions of optical biomedical imaging on living cells.

See the news on the CNRS website

These researches have been published on Journal of American Chemical Society

Patrick F. Muldoon, Guillaume Collet, Svetlana V Eliseeva, Tian-Yi Luo, Stephane Petoud, and Nathaniel L Rosi. Ship-in-a-bottle preparation of long wavelength molecular antennae in lanthanide metal-organic frameworks for biological imaging. J. Am. Chem. Soc. (2020) 142, 8776-8781 - doi : 10.1021/jacs.0c01426

Manganese: A double agent for imaging ?

Gadolinium (Gd3+) complexes have been used as MRI contrast agents for 35 years, but recently the safety of some was questioned. The replacement of Gd3+ by manganese (Mn2+), a biogenic metal, would enable safer complexes.

Nevertheless, the Mn2+ has to be chelated by complexes exhibiting high thermodynamic stability and kinetic inertness (to guarantee that the Mn is not released in vivo) and with a water molecule directly coordinated to the metal, essential for a good MRI efficiency. Combining these two properties is a chemistry challenge.

The “Metal complexes and MRI” team of CBM and their collaborators from IPHC (Strasbourg) have synthesized and studied a bispidine ligand, a molecule which cavity is well adapted for Mn2+ complexation. This Mn2+ complex has an excellent kinetic inertness and its MRI efficiency was validated by preclinical studies.

52Mn is an emergent radionuclide for positron emission tomography (PET). Mn2+ is the only metal enabling both MRI and PET imaging. The use of 52Mn is nevertheless limited by its low availability and lack of appropriate ligand.

For the first time in France, 52Mn was produced at the Orléans’ cyclotron, and 52Mn-bispidine was successfully obtained.

Overall, bispidine is a very promising ligand for the Mn2+ complexation, for MRI and PET. Due to its outstanding kinetic inertness, in vivo use of Mn2+ without toxicity risk can be anticipated.

 

See the news on the website of the CNRS Institute for Chemistry.

 

Eva Toth, Daouda Ndiaye, Maryame Sy, Agnès Pallier, Sandra Même, Isidro de Silva, Sara Lacerda, Aline M. Nonat, Loïc J. Charbonnière Unprecedented kinetic inertness for a Mn2+‐bispidine chelate: a novel structural entry for Mn2+‐based imaging agents - Angewandte Chemie, 2020, https://doi.org/10.1002/anie.202003685