First Evaluation of a 99mTc-Tricarbonyl Complex, 99mTc(CO)3(LAN), as a New Renal Radiopharmaceutical in Humans

Journal of Nuclear Medicine

Eugene Malveaux¹  Xiaolong Xu¹  Haiyang He¹  Andrew Taylor¹  Luigi G. Marzilli¹  Malgorzata Lipowska¹ 

关键词: ^99mTc-tricarbonyl;    lanthionine;    ^99mTc(CO)₃(LAN);    renal radiopharmaceuticals;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

99mTc-Mercaptoacetyltriglycine (99mTc-MAG3), 99mTc-dd- and ll-ethylene-dicysteine (99mTc-EC), and 99mTc-mercaptoacetamide-ethylene-cysteine (99mTc-MAEC) contain N3S or N2S2 ligands designed to accommodate the 4 ligating sites of the (99mTcO)3+ core; they are all excellent renal imaging agents but have renal clearances lower than that of 131I-orthoiodohippurate (131I-OIH). To explore the potential of the newly accessible but less polar [99mTc(CO)3]+ core with 3 ligating sites, we decided to build on the success of 99mTc-EC, with its N2S2 ligand and 2 dangling carboxylate groups; we chose an N2S ligand that also has 2 dangling carboxylate groups, lanthionine, to form 99mTc(CO)3(LAN), a new renal radiopharmaceutical. Methods: Biodistribution studies were performed on Sprague–Dawley rats with 99mTc(CO)3(LAN) isomers, meso-LAN and dd,ll-LAN (an enantiomeric mixture), coinjected with 131I-OIH. Human studies also were performed by coinjecting each 99mTc-labeled product (∼74 MBq [∼2 mCi]) and 131I-OIH (∼7.4 MBq [∼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 131I-OIH. In humans, both agents provided excellent renal images, with the plasma clearance averaging 228 mL/min for 99mTc(CO)3(meso-LAN) and 176 mL/min for 99mTc(CO)3(dd,ll-LAN). At 3 h, both 99mTc(CO)3(meso-LAN) and 99mTc(CO)3(dd,ll-LAN) showed good renal excretion, averaging 85% and 77% that of 131I-OIH, respectively. Plasma protein binding was minimal (10% and 2%, respectively), and erythrocyte uptake was similar (24% and 21%, respectively) for 99mTc(CO)3(meso-LAN) and 99mTc(CO)3(dd,ll-LAN). Conclusion: Although the plasma clearance and the rate of renal excretion of the 99mTc(CO)3(LAN) complexes were still lower than those of 131I-OIH, the results of this first application of a 99mTc-tricarbonyl complex as a renal radiopharmaceutical in humans demonstrate that 99mTc(CO)3(LAN) complexes are excellent renal imaging agents and support continued renal radiopharmaceutical development based on the 99mTc-tricarbonyl core.

【 授权许可】

Unknown