Such class of agents is based on the magnetization transfer of saturation on the water NMR signal. The amount of such a transfer depends on a number of factors (number of exchangeable protons in the CEST agent and their rate of exchange, intensity of the saturating RF field, ... ). The following activities are under development:
- Observation of more agents in the same anatomical region
Non-spherical liposomes that contain chemical shift agents both in the inner cavity and on the membrane are used. We have already demonstrated that such category of liposomes (LipoCEST) is particularly suited because it produces big shifts of the intraliposomial water proton resonance; the latter are well accepted as they permit to exploit high values of the exchange rate K ex. The aim of the research is to produce a series of systems that differ for the irradiation frequency; they will be used both unmodified and functionalized in order to make them responsive to particular targets.
- Iopamidol as a CEST agent
Iopamidol is one of the most used contrast agent for X-ray CT scans. It contains three iodine atoms (that makes it an X-ray opaque agent) and three amides functionalities that could act as a pool of exchanging protons, making it a potential CEST agent. Being it a diamagnetic species, the amide chemical shifts are near to the water chemical shift and this feature could potentially harm its role as a CEST agent, because of the extensive direct saturation of the water signal. We then carefully adjusted the acquisition of the images and developed post-processing procedures in order to definitely extract its true CEST contribution to the image. For the sake of sensitivity, the target organ was identified in the kidney, being the region where iopamidol accumulates prior to urinary excretion. The possibility to develop a protocol to quantitatively extract the efficacy of glomerular filtration on a voxelwise basis is under intense scrutiny.
- Diagnostics based on water diffusing from CEST containing
The intrinsic mechanism of action of the CEST agents implies that the effect itself could be observed not only in the voxels where the agent distributes, but also from voxels that do not contain any quantity of the agent. The effective observation of such phenomenon depends on a number of factors such as the duration of the irradiation, the CEST agent concentration, the existence of favorable diffusion pathways ... It is our intention to develop diagnostic agents and protocols that exploit this peculiar characteristic of the CEST effect.
- T2 vs CEST: a method for macrophages uptake determination
Liposomes loaded with paramagnetic complexes could act both as T 2*and as CEST agents. However, when these agents are captured by macrophages, the CEST effect is lost, while the T 2*contribution to the image remains. It then follows that by comparing the CEST vs. the T 2*effects in the MRI images, a map of the macrophages sequestration activity could in principle be obtained.
The main problem dealing with the use of LipoCEST agents, is their limited blood half-life time because of the sequestration by macrophages. For targeting applications it is then essential to develop new systems with longer blood half-life time. Polymersomes could represent useful alternatives to liposomes for these applications; they are made of block-polymers (containig both lipophilic and hydrophilic regions) that tack together in way similar to phospholipids in the membranes of liposomes. It has been verified that polymersomes loaded with paramagnetic chemical shift reagents could be a real alternative to in vivoLipoCEST agents. We are now trying to transfer this on the in vivoside.