Friday, April 15, 2011
Targeted Delivery of Molecular Probes for In Vivo Electron Paramagnetic Resonance Imaging (EPRI)
Univ. of Maryland School of Medicine
The imaging modality: Magnetic resonance imaging (MRI) depends on the detection of protons, which are vastly abundant in the body. In contrast, EPRI detects molecules bearing unpaired electrons — i.e., free radicals—which are normally extremely short-lived and scarce in the body. Therefore, to visualize specific tissues by EPRI, so-called “spin probes”, which are stable free radicals such as nitroxides, must be targeted to the tissue of interest.
The delivery vehicle for imaging probes: Nano-immuno-liposomes (NILs) are nanometer-scale lipid vesicles bearing antibody fragments that target tumor cells specifically. NILs can encapsulate nitroxides at concentrations in excess of 0.1 M, at which their spectroscopic signal is self-quenched. (This is analogous to the concentration-dependent quenching of fluorescent molecules.) Thus intact NILs are spectroscopically “dark” and invisible by EPRI.
Generation of image contrast: When injected into the circulation, NILs “find” and bind to tumor cells, which take up the vesicles by endocytosis. Once inside a tumor cell, NILs are metabolized and the nitroxides they contain are liberated and greatly diluted into the cell volume. The consequent “de-quenching” of nitroxides generates a robust intracellular EPR signal, which makes the tumor cells “bright” and visible by EPRI.
I will discuss all aspects of this imaging approach, from the spectroscopic basis of magnetic imaging, through the design and chemical synthesis of the nitroxide imaging probes, to actual application in living animals.
(Joint with Biological Sciences)
Refreshments at 4:00 PM. Seminar begins at 4:10 PM.
Building 8, Room 241
For further information, please call (909) 869-4014