Synthesis of contrast agents
The synthesis of an imaging probe is the first step of the process of a molecular imaging investigation. The optimization of innovative imaging probes can be pursued through
different approaches: from the design of imaging units endowed with enhanced sensitivity, to the development of high-affinity ligands and their conjugation to the targeting vector,
and to the control of the structural and electronic determinants responsible for the molecular recognition of the target molecule.
Importantly, in case of metal-based imaging reporters, the observation of toxic effects related to fast release of the metal ion from the corresponding complex committed our research
towards the use and modification of chelates with high thermodynamic stability and most of all high kinetic inertness to allow their safe in vivo application.
A more detailed explanation of the synthetic approaches developed in our laboratories is listed below:
- Nanosystems and targeting agents
In the group, various nanosystems such as liposomes, micelles, proteins and polymeric nanoparticles (PLGA) for diagnostic and/ or theranostic applications are investigated. Although, nanoparticles passively accumulate in tissue inflammation or cancer, as a consequence of the EPR effect, internalization e.g. by endocytosis, ofsuch nanosystems can be greatly improved by attachment of a high-affinity targeting ligand.To functionalize the particles for targeting, it is necessary to append reactive functional groups to the surface, to allow conjugation to vectors such as antibodies, peptides, small molecules. Another approachis to prepare newly phospholipid-based vectors, by conjugation of peptides, folic acid, high afinity ligands to DSPE-PEG2000 and, subsequently, use to formulate targeted lipid-based nanosystems.
- MRI and SPCCT Multimeric contrast agents
Design and synthesis of multimeric polyaminocarboxylate ligands for complexation of paramagnetic Gd3+ ions as contrast agents (CAs) for Magnetic Resonance Imaging (MRI) and for Spectral Photon-Counting Computed Tomography (SPCCT) having Gd3+ almost ideal physico-chemical properties in terms of K-edge absorption energy to behave as a CA for SPCCT. The synthesis of improved multimeric CAs greatly enhance the sensitivity of both imaging techniques. Typical approach is the attachment of a number of Gd-chelates to multimeric-dendrimerics tructures like poliamidoamine or branched poly(lysine).
- Molecular Imaging Probes
A molecular imaging probe typically consists of a signaling agent, a targeting moiety, and a linker. Various types of linkers can be used to modulate the pharmacokinetics and the selectivity of the imaging probe (the length, flexibility, hydrophilicity, and charges). Many aspects need to be optimized to obtain an efficient probe for MRI and nuclear medicine techniques (PET and SPECT): we use various bioconjugation approaches and different BFCAs (bifunctional chelating agents) for connecting metal complexes to targeting vectors. For optical bioluminescence/fluorescence imaging, near infrared (NIR) optical dye such as sulfoCy5.5 are coupled with targeting moiety.
- CEST and hyperpolarized agents
Also Chemical Exchange Saturation Transfer (CEST) MRI applications often requires the synthesis of probes able to enhance the effect and allow the in vivo application. Several Ln(III) chelates optimized for this type of imaging technique are synthesized in our labs. Similarly, 13C labelled unsaturated small molecules involved in particular metabolic processes are also synthesized as hyperpolarized probes for para-hydrogen polarization method.
- Contrast agents for Photoacoustic Imaging (PAI)
Hemoglobin and melanin are the two most important naturally occurring contrast agents to enhance photoacoustic effect. Melanin can be used as exogenous PAI CA only after preparation of highly water-soluble systems by fabrication of ultrasmall melanin nanoparticle with good dispersion stability, e.g. MFA (melanin free acid) starting from melanin granules through a slight degradation after oxidative treatments.