DEVELOPMENT OF NEW RENAL FUNCTION IMAGING AGENTS

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None of the existing radiopharmaceuticals for measuring renal function in humans accurately measures effective renal plasma flow. The two commercially used agents exhibit extraction efficiencies of only .80 and .65 times that of the ideal substrate para-amino hippuran (PAH). A new prototype hydrophilic penta-anionic complex [Technetium (Carboxy- methyl-isocyanide)6]-5 (Tc-CAMI) has been synthesized and evaluated in animals. The surface of this metal complex contains six symmetrically arranged carboxylic acid groups that can act as substrates for the organic anion receptor affording tubular secretion of this prototype agent. Biodistribution in mice and rabbits showed this compound to have similar blood clearance and distribution to 99mTC-MAG3 and 131I-hippuran but a slower clearance into the urine and higher residual kidney activity. In dogs, dynamic gamma camera imaging of 99mTc-CAMI when compared with proven tubular secretion agent 99mTC-MAG3 and glomerular filtration agents (99mTC-DTPA) showed the fastest blood clearance but slightly slower excretion into the urine. These experiments and data that probenecid competes with 99mTc-showed the fastest blood clearance but slightly slower excretion into the urine. These experiments and data that probenecid competes with 99mTc-CAMI for renal transport indicates that this compound is functioning as a tubular secretion agent, although not as effective as the "gold standard" PAH. PROPOSED COMMERCIAL APPLICATIONS: None of the current radiopharmaceuticals for measuring renal function in humans accurately measures effective renal plasma flow. A more efficiently excrete renal agent would increase the accuracy of clinical diagnosis and lower the cost through competitive pricing.