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  • Title: First evaluation of a 99mTc-tricarbonyl complex, 99mTc(CO)3(LAN), as a new renal radiopharmaceutical in humans.
    Author: Lipowska M, He H, Malveaux E, Xu X, Marzilli LG, Taylor A.
    Journal: J Nucl Med; 2006 Jun; 47(6):1032-40. PubMed ID: 16741314.
    Abstract:
    UNLABELLED: (99m)Tc-Mercaptoacetyltriglycine ((99m)Tc-MAG3), (99m)Tc-dd- and ll-ethylene-dicysteine ((99m)Tc-EC), and (99m)Tc-mercaptoacetamide-ethylene-cysteine ((99m)Tc-MAEC) contain N(3)S or N(2)S(2) ligands designed to accommodate the 4 ligating sites of the ((99m)TcO)(3+) core; they are all excellent renal imaging agents but have renal clearances lower than that of (131)I-orthoiodohippurate ((131)I-OIH). To explore the potential of the newly accessible but less polar [(99m)Tc(CO)(3)](+) core with 3 ligating sites, we decided to build on the success of (99m)Tc-EC, with its N(2)S(2) ligand and 2 dangling carboxylate groups; we chose an N(2)S ligand that also has 2 dangling carboxylate groups, lanthionine, to form (99m)Tc(CO)(3)(LAN), a new renal radiopharmaceutical. METHODS: Biodistribution studies were performed on Sprague-Dawley rats with (99m)Tc(CO)(3)(LAN) isomers, meso-LAN and dd,ll-LAN (an enantiomeric mixture), coinjected with (131)I-OIH. Human studies also were performed by coinjecting each (99m)Tc-labeled product ( approximately 74 MBq [ approximately 2 mCi]) and (131)I-OIH ( approximately 7.4 MBq [ approximately 0.2 mCi]) into 3 healthy volunteers and then performing dual-isotope imaging by use of a camera system fitted with a high-energy collimator. Blood samples were obtained from 3 to 90 min after injection, and urine samples were obtained at 30, 90, and 180 min. RESULTS: Biodistribution studies in rats revealed rapid blood clearance as well as rapid renal extraction for both preparations, with the dose in urine at 60 min averaging 88% that of (131)I-OIH. In humans, both agents provided excellent renal images, with the plasma clearance averaging 228 mL/min for (99m)Tc(CO)(3)(meso-LAN) and 176 mL/min for (99m)Tc(CO)(3)(dd,ll-LAN). At 3 h, both (99m)Tc(CO)(3)(meso-LAN) and (99m)Tc(CO)(3)(dd,ll-LAN) showed good renal excretion, averaging 85% and 77% that of (131)I-OIH, respectively. Plasma protein binding was minimal (10% and 2%, respectively), and erythrocyte uptake was similar (24% and 21%, respectively) for (99m)Tc(CO)(3)(meso-LAN) and (99m)Tc(CO)(3)(dd,ll-LAN). CONCLUSION: Although the plasma clearance and the rate of renal excretion of the (99m)Tc(CO)(3)(LAN) complexes were still lower than those of (131)I-OIH, the results of this first application of a (99m)Tc-tricarbonyl complex as a renal radiopharmaceutical in humans demonstrate that (99m)Tc(CO)(3)(LAN) complexes are excellent renal imaging agents and support continued renal radiopharmaceutical development based on the (99m)Tc-tricarbonyl core.
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