CEST and PARAC EST Agents for Molecular Imaging - The Chemistry of Molecular Imaging - page 241

These properties can easily be fine-tuned by varying the molecular weight and microstructure of the block copolymer.
Polymersomes entrapping high amounts of TmDOTMA have also been prepared and their ability to generate CEST contrast
has been assessed in vitro . Interestingly, polymersomes behaved like liposomes in terms of chemical shift of intravesicular
protons, contrast efficiency, and sensitivity of the nanovesicles to osmotic changes [82].
In the recent years other nanosised particles such as micelles [83], dendrimers [84], silica- [85,86], polymer- [87], and
perfluorocarbon nanoparticles [88], have been considered as carriers of PARACEST agents. Additional innovative applica-
tions of such systems have been further explored (e.g. see Ref. [87]).

10.8 concluSIonS

CEST agents have origins from the well-established magnetisation transfer (MT) phenomenon widely exploited both in high
resolution NMR spectroscopy and MRI. Compared to MT effects, CEST effects are characterised by more defined NMR sig-
nals, which allows selective RF irradiation. The availability of these frequency-encoding agents allows the setup of experiments
in which the contrast in the MR image is generated 'at will' only if the appropriate frequency corresponding to the labile protons
of the exogenous agent is irradiated. This approach offers the possibility of detecting more than one agent in the same region,
thus allowing for multiplex detection that is not permitted with classical relaxation enhancers based on Gd(III) complexes or
iron oxide particles. Furthermore, the acquisition of a pre-contrast image may no longer be necessary because the CEST contrast
results from the acquisition of two post-contrast experiments simply differing in the on/off switch of the irradiation RF field.
Another important advantage that CEST agents have over conventional relaxation agents is the possibility of designing
responsive agents whose MRI signal can be made independent of the probe concentration. Although the poor sensitivity of
small-molecule CEST agents may still present a problem for molecular imaging applications, the design of supramolecular
and nanosized systems with much lower detection limits could potentially resolve this issue. The increasing number of
scientific reports on the CEST topic supports the view that this new family of MR contrast agents can certainly be considered
as one of the most interesting innovations that has come out in the field of MRI contrast media development in the recent years.

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