H2020Индивидуална стипендия2021–2026

tZR-CA-InVivo · Targeted contrast agents to better detect pancreatic tunor and its zinc content by MRI on mice

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-11-01 → 2026-12-27
Финансиране от ЕС: 196 708 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Специални контрастни вещества за ЯМР изследват нивата на цинк в тумори на панкреаса при мишки. Разбирането на тези процеси помага за откриване на ранни биомаркери и разработване на по-ефективни методи за диагностика на заболявания.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Targeted contrast agents to better detect pancreatic tunor and its zinc content by MRI on mice

Zinc is an essential tightly regulated d-block metal ion, which has anti-oxidant effects. However, a deficiency or overload in zinc is pro-oxidant and even cytotoxic. Misregulation of zinc homeostasis has been implicated in various diseases such as neurodegenerative diseases (Alzheimer, Parkinson), diabetes, and cancers (prostate, breast, hepatocellular and pancreatic). Understanding the zinc biodistribution during the development of the disease would: (1) help understanding the molecular mechanisms at the origin of the disease; (2) proposing zinc as an early biomarker of the disease, and (3) finding a potential zinc treatment. The development of Gd-based contrast agents for Zn detection is a rapidly growing field, pioneered by the success of a Gd-DOTA derivative that was successfully used in vivo diabetes model or for the early detection of prostate cancer. This contrast agent responds to zinc in the presence of Human Serum Albumin (HSA), the major extracellular protein in the blood. The major changes are obtained in vitro at medium magnetic fields (0.5-1.5 T), while this contrast agent works perfectly in vivo at higher field where the resolution is better (7-9.4 T). Therefore, the mechanisms at the origin of the in vivo response are not clear. It would be very important to understand them in order to develop more efficient contrast agents. Indeed, the search of more efficient agents would allow to access lower zinc concentration, and therefore better detect zinc fluctuations for early detection, and treatment of diseases. We have tackled this problem in two ways: (1) study in detail the interaction of the contrast agent with HSA; (2) understand in vitro the molecular parameters at the origin of the response.

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

Цел на проекта

Pancreatic cancer has the lowest survival rate Pancreatic cancer has the lowest survival rate of all cancers in Europe, the median survival time is only a few months due to the lack of test for early diagnosis, and no effective therapies for metastatic forms. Pancreatic Ductal Adenocarcinoma (PDAC), like prostate and hepatocellular cancers present a down regulation of zinc importers and low zinc content. Treatment with clioquinol, a zinc ionophore, to increase the amount of zinc in the tumor has shown to inhibit tumor growth. This project aims at creating new tool to better detect PDAC by Magnetic Resonance Imaging, and the evaluation of di zinc ionophore to elevate the content in zinc in the tumor environment. Using the same modular approach, a normal and a zinc responsive contrast agent targeted to the PDAC will be synthesized by conjugation of a peptidic sequence known to target the tumor bearing a Single Core Multimodal Imaging Platform for quantification, with a peptide functionalized with a normal or zinc responsive contrast agent. After careful characterizations in vitro and ex vivo, they will be used in mice implanted with orthoptic pancreatic tumors. One of the projects developed by the “Metallic complexes for MRI” group, consist designing and using MRI probe for various substrates, including zinc. The group masters all the techniques to characterize the contrast agents, and the experience researcher (ER) will bring the knowledge about zinc biology, and infrared microscopy to quantify the contrast agent in tissues. Benefiting from the competitive interdisciplinary environment of CBM, and within the group, the ER will acquire new technical skills, knowledge and network the frontier between chemistry, biology and MRI imaging, in particular working with animal model (mice), to adequately implement the project and complete her skill set to become an independent researcher interested in developing tools to study the role of metals in biological context.

Оригинален текст от CORDIS (на английски).

Участници

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisКоординаторФранция