Project description
Advancing MRI safety with iron-based contrast agents
Magnetic resonance imaging (MRI) is essential for early disease diagnosis and treatment monitoring. However, the gadolinium-based contrast agents (Gd-CAs) used in MRI raise significant safety and environmental concerns. The challenge lies in finding a viable alternative that is both effective and non-toxic. Iron (Fe(III)) porphyrins show promise, but are hindered by issues like μ-oxo-dimer formation, which reduces their efficacy. With the support of the Marie Skłodowska-Curie Actions programme, the PorphIRON project aims to overcome these limitations by developing new iron-based contrast agents. By optimising the structure of Fe(III) porphyrins, PorphIRON will enhance their stability and effectiveness while ensuring biocompatibility. This project combines advanced porphyrin chemistry with computational studies and MRI expertise to create safe, high-performance contrast agents for future clinical use.
Objective
Magnetic resonance imaging (MRI) plays a pivotal role in early diagnosis and therapy follow-up of many diseases. The substitution of current Gd-based MRI contrast agents (CA), which raise both safety and environmental concerns, is one of todays most important challenges in imaging-related chemistry. High complex stabilities and inertness attainable with Fe(III) make it a high potential alternative to Gd. Porphyrins have met great clinical success, exhibit biocompatibility, stable metal complexes and easy structural modulation., but formation of -oxo-dimers in Fe(III) porphyrins (FePo) reduces their relaxation efficacy. PorphIRON will tackle these limitations and develop new families of biocompatible FePo fine-tuned for MRI use. PorphIRON will focus on structural optimization to i) maintain the oxidation and the high spin state of Fe(III), yielding relaxation effect comparable to clinical CA, and ii) adjust physicochemical properties to preserve biocompatibility. To achieve this, PorphIRON will rely on a synergic combination of the ERs experience in porphyrin chemistry and computational studies with that of the supervisor in MRI CA development, and an iterative approach with: i) initial synthesis of newly designed FePo, followed by their physicochemical and biological evaluation; ii) computational rationalization of the experimental results and prediction of new optimized structures; iii) second-round optimized FePo synthesis and characterization. PorphIRON will deliver fully characterized, stable, biocompatible and high efficacy FePos with preliminary preclinical in vivo MRI validation, thereby actively contributing to the implementation of next-generation non-toxic CA in clinic. PorphIRON will strengthen ERs experience in organic synthesis, computational chemistry, while significantly expanding his knowledge to CA development and preclinical MRI. It will expand his career perspectives and open new opportunities in the emerging field of theragnostics.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2023-PF-01
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75794 Paris
France
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