"Magnetic resonance imaging (MRI) has become an indispensable medical diagnostic tool because of its ability to produce detailed 3D pictures of tissue in the body noninvasively. Gadolinium is used in MRI contrast agents because of its strong paramagnetic properties. However, due to its intrinsic toxicity when free in solution, it has to be bound to other biocompatible molecules to be used clinically. There are currently seven approved gadolinium contrast agents that are used for MRI studies in humans. However, these contrast agents have some drawbacks: e.g. they are not targeted to specific tissues and their sensitivity is still below what can be theoretically achieved. Therefore, there is great current interest in improving the properties of Gd-based contrast agents by attaching the metal to a variety of materials, ranging from large organic molecules to nanoparticles.
Phosphatidylserine (PS) is the most abundant anionic phospholipid of the plasma membrane and, in healthy cells, is arranged largely on the inner layer. In some abnormal cells this is not the case and a considerable amount of PS is displayed on the outer membrane surface; this is known in cells undergoing apoptosis (programmed cell death) and tumour vasculature. Therefore, detection and imaging of apoptotic cells in vivo is desirable, as a clinical and research tool. Recently the host group showed that a Gd metal complex is able to bind polyphosphates and, interestingly, the probe localises selectively on apoptotic cells allowing for enhanced MRI signal in apoptotic vs. non-apoptotic cells. To follow on this previous work, we propose to develop more sensitive and selective Gd-based probes for MR imaging of apoptosis. Furthermore we propose to extend this idea towards positron emission topography (PET) by including Ga in the probes. The new probes developed, will be first fully characterised and validated in in vitro experiments to then be tested against apoptotic and non-apoptotic cell lines."
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