HEPATOCYTE DIRECTED MAGNETIC RESONANCE CONTRAST AGENTS

DISEASES OF THE LIVER ARE A MAJOR HEALTH PROBLEM. DIAGNOSTIC TECHNIQUES TO PREDICT LIVER FAILURE ARE INTERPRETABLE IN TERMS OF OVERALL LIVER FUNCTION, NOT IN TERMS OF ANATOMIC STRUCTURE. ANATOMICAL INFORMATION ON LIVER HAS BEEN OBTAINED BY USING RADIOACTIVE COLLOIDS. THESE MATERIALS ARE TAKEN UP BY KUPFFER CELLS (3% OF LIVER MASS) AND NOT BY HEPATOCYTES (90% OF LIVER MASS), THE MAIN METABOLIZING CELL OF THE LIVER. CURRENT IMAGING MODALITIES INCLUDING MR AND CT ARE ALSO OF LIMITED USEFULNESS IN DEFINING FUNCTIONING LIVER VOLUMES. TO OVERCOME THESE DIAGNOSTIC LIMITATIONS, THE SYNTHESIS AND CHARACTERIZATION OF GALACTOSE CONTAINING MAGNETICALLY LABELLED PROTEINS (BOTH SOLUBLE AND PARTICULATE) IS PLANNED. THESE PROTEINS, DIRECTED TO THE ASIALOGLYCOPROTEIN RECEPTOR OF HEPATOCYTES BY GALACTOSE, ARE EXPECTED TO SIGNIFICANTLY EFFECT TISSUE PROTON RELAXATION RATES AND THEREBY DEFINE FUNCTIONING LIVERMASSES ON MR IMAGES. RECEPTOR TARGETED MR CONTRAST AGENTS REPRESENTS A TECHNOLOGICALLY NOVEL AND POTENTIALLY GENERAL APPROACH TO THE DESIGN OF MR CONTRAST AGENTS.