Recently, a team at the SCBM developed diagnostic nanometric micellar vectors for in vivo tumor targeting and visualization by fluorine-19 MRI (see the 2021 news: Institut des sciences du vivant Frédéric Joliot – A micellar probe for tumor imaging by fluorine magnetic resonance). These vectors feature a central reservoir for encapsulating a perfluorinated probe such as PERFECTA (suPERFluorinatEd ContrasT Agent), one of the few probes easily detectable by MRI but insoluble in water, which compromises its biocompatibility. In collaboration with a team from BAOBAB (NeuroSpin) and the Department of Cellular and Molecular Radiobiology (CEA-Jacob), the researchers showed that these vectors allow in vivo visualization of tumor areas through passive accumulation. However, they present a drawback: the micelles also accumulate transiently in the liver, generating a strong signal that reduces contrast in the regions of interest.
The SCBM team therefore envisioned a new version of the micelles that would allow selective switching off of the MRI signal in non-pathological areas. The researchers co-encapsulated a photoactivatable ferrocene derivative together with PERFECTA. In its initial state, ferrocene does not affect the MRI signal, allowing visualization of the micelle (“On" state). Upon light irradiation, the ferrocene is oxidized into a paramagnetic species that causes a decrease in the MRI signal of the PERFECTA contained in the micelle (“Off" state).
This extinction principle was validated in vitro, with a tenfold reduction in the MRI signal associated with PERFECTA within the micelle after illumination. While this new tool opens the way to precise spatial and temporal control of MRI contrast, the blue light used to activate the ferrocene penetrates poorly into biological tissues. This implies that future work must focus on designing probes activatable in the near-infrared, a more tissue-penetrant light, in order to make this new tool applicable to in vivo preclinical studies.
Contacts Institut des sciences du vivant Frédéric-Joliot :