Target specific MRI contrast agents
The in vivo visualization of molecular markers of disease processes with the use of MRI is a major challenge, for two reasons. First, the biomarkers of interest often occur in relatively low concentrations. Second, MRI is a relatively insensitive technique. It is our ambition to develop powerful MRI contrast agents that, upon binding to the wanted target, produce sufficient local MRI signal change to allow the in vivo visualization of the target distribution.
Figure 1 shows a schematic representation of liposome for multi-modality molecular imaging. The liposomes contain paramagnetic lipid and fluoresencent lipid for MRI contrast and fluorescence microscopy validation, respectively. Other components including cholesterol are mixed in to create stable vesicular structures, while PEG-containing lipids are added to achieve long blood half lifes. Ligands are conjugated to the distal end of PEG chains for targeting to the biomarker of interest.
Next to contrast agents, we develop novel MRI detection schemes, with which low concentrations of contrast agents can be more sensitively detected.
There are several classes of MRI contrast agents that are suitable for target specific MRI. Our research focusses on paramagnetic nano-particles that contain a high payload of Gd(III)-containing chelates (predominantly used for their ability to shorten the longitudinal relaxations time T1) and on superparamagnetic FeO nano-particles (mainly used for their strong T2/T2*-shortening effects).
Strijkers GJ, Mulder WJM, Van Tilborg GAF, and Nicolay K. MRI contrast agents: current status and future perspectives. Anti-Cancer Agents in Medicinal Chemistry 7: 291-305, 2007.
Van Tilborg GAF, Mulder WJM, Deckers N, Storm G, Reutelingsperger CP, Strijkers GJ, and Nicolay K. Annexin A5-functionalized bimodal lipid-based contrast agents for the detection of apoptosis. Bioconj Chem 17, 741-749, 2006.
Mulder WJM, Strijkers GJ, Van Tilborg GAF, Griffioen AW, and Nicolay K. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed 19: 142-164, 2006.
Mulder WJM, Koole R, Brandwijk RJ, Storm G, Chin PTK, Strijkers GJ, De Mello Donegá, Nicolay K, and Griffioen AW. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Letters 6: 1-6, 2006.
Mulder WJM, Strijkers GJ, Griffioen AW, Van Bloois L, Storm G, Koning GA, and Nicolay K. A liposomal system for contrast-enhanced MR imaging of molecular targets. Bioconjug Chem 15: 799-806, 2004.