HEИндивидуална стипендия2022–2024

PARA-FLUOR · Paramagnetic, fluorinated and water-soluble metal complexes for 19F MRI

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2022-10-01 → 2024-09-30
Финансиране от ЕС: 211 755 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Метални комплекси с флуор и парамагнитни йони се разработват за подобряване на изображенията при ЯМР с флуор-19, например за проследяване на клетки в тялото. Това помага за преодоляване на проблемите с ниската разтворимост и слабия сигнал на сегашните методи за диагностика.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Paramagnetic, fluorinated and water-soluble metal complexes for 19F MRI

19F MRI has emerged recently as a complementary technique to classical, 1H-based MRI. Given the lack of background signal, 19F MRI is very attractive for various biomedical applications, including in vivo cell tracking. However, it also has many limitations, mainly related to low solubility, low stability, low sensitivity and relatively long 19F relaxation times of current 19F MRI probes, which are mostly based on polyfluorinated compounds. This project aimed to overcome these drawbacks by developing highly water-soluble, stable and kinetically inert metal complexes. They consist of small molar weight (< 1000 Da), 19F containing ligands and paramagnetic metal ions (Mn(II) or Fe(III)) which largely shorten 19F relaxation times, thereby maximizing the 19F MRI signal to noise ratio achievable in a given timeframe. Building on the optimal relaxation properties of paramagnetic iron and manganese ions and on the strong expertise of the candidate and the host group in Mn(II) and Fe(III) coordination chemistry, the project’s goal was to specifically address the major current bottlenecks of 19F MRI by developing 19F probes which (i) avoid solubility, stability and biodistribution problems associated with nanoemulsions, and (ii) maximize 19F MRI signal to noise ratio by using efficient relaxation agents. We aimed at combining, for the first time, advantageous paramagnetic properties of Mn(II)/(III) or Fe(II)/(III) and small molar weight molecules which have sufficient 19F content for MRI detection to create water soluble, highly stable and inert complexes endowed with short 19F relaxation times and good biocompatibility. This requires structural optimization by integrating 19F atoms in the complex at an optimized distance from the metal ion in order to allow for fast relaxation without extensive broadening of the 19F NMR peaks that would cause signal vanishing in MRI. Additionally, we also aimed at designing probes, which are efficient not only in 19F MRI, but can combine detection capabilities in both 19F and classical 1H MRI.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

19F MRI relies mainly on the use of fluorine-dense perfluorocarbon nanoemulsions. However, poor water solubility, limited stability, droplet heterogeneity, rigorous liver accumulation of the particles, as well as the relatively long fluorine relaxation times often limit their applicability. Fe(III) and Mn(II) have the most advantageous paramagnetic properties to shorten T1 relaxation time of 19F without strong line-broadening T2 effect, deleterious for 19F MRI detection. The combination of these paramagnetic metal ions with small molecular weight ligands containing maximized number of magnetically equivalent fluorine atoms is proposed here to circumvent the problems associated with perfluorocarbon nanoemulsions. We will create complexes that provide high thermodynamic stability and kinetic inertness important for safe biological application, good water solubility, as well as short 19F T1 relaxation time, allowing for fast MRI scans and high signal to noise ratio. A series of open-chain and macrocyclic ligands will be synthetized and their Mn(II) and Fe(III) complexes characterized with respect to their application as 19F MRI agents (water solubility, thermodynamic and kinetic stability, 19F relaxation properties). Structural variations of the ligands will allow for optimizing the 19F-metal distance for optimized relaxation effect. For a proof of concept cell labelling study, we will choose dendritic cells (DC) and T lymphocytes (TL), two cell types frequently used for adoptive cell transfer strategies in oncology. Cytotoxicity and cell labelling capacity of the probes will be assessed and in vitro MRI phantom images will be acquired on cells labelled with the paramagnetic complexes.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция