RECEPTOR DIRECTED SUPERPARAMAGNETIC MRI CONTRAST AGENTS

THE ULTIMATE GOAL OF THIS RESEARCH IS THE DEVELOPMENT OF TISSUE SPECIFIC, OR DIRECTED MAGNETIC RESONANCE UMAGING (MRI) CONTRAST AGENTS. THESE AGENTS WILL CONSIST OF PEPTIDES ATTACHED TO SMALL, BIODEGRADABLE SUPERPARAMAGNETIC IRON OXIDE COLLOIDS. THE BIODISTRIBUTION OF THE SUPERPARAMAGNETIC IRON OXIDE LABEL WILL BE DETERMINED BY THE PEPTIDE ON THE SURFACE OF THE IRON OXIDE AND BY THE PRESENCE OF SPECIFIC RECEPTORS IN A TARGET TISSUE. THE DEVELOPMENT OF SUCH AGENTS WILL INCREASE THE ALREADY CONSIDERABLE DIAGNOSTIC POWER OF MRI. IN PHASE I, PEPTIDE HORMONES WITH RECEPTORS IN PANCREATIC TISSUE WILL BE ATTACHED TO SUPERPARAMAGNETIC IRON OXIDE PARTICLES AND SUCCESSFUL TARGETING TO THE PANCREAS DEMONSTRATED. THE PANCREAS IS OUR INITIAL TARGET ORGAN BECAUSE IT POSSESSES RECEPTORS FOR A NUMBER OF LOW MOLECULAR WEIGHT PEPTIDE HORMONES (E.G. SOMATOSTATIN, CHOLECYSTOKININ, VASOACTIVE INTESTINAL PEPTIDE, SECRETIN, AND CRP/BOMBESIN). PANCREATIC CANCER HAS A HIGH MORTALITY RATE DUE IN PART TO DIFFICULTIES IN ASSESSING THE PATHOLOGY OF THE PANCREAS BY STANDARD IMAGING METHODS, SUCH AS CT OR MRI.