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

• Authors: Malgorzata Lipowska, Emory University; Haiyang He, Emory University; Eugene J Malveaux Sr., Emory University; Xiaolong Xu, Emory University; Luigi G. Marzilli, Louisiana State University; Andrew T Taylor Jr., Emory University
• Journal Title: Journal of Nuclear Medicine and Radiation Therapy
• Volume: Volume 47, Number 6
• Publisher: Society of Nuclear Medicine | 2006-06, Pages 1032-1040
• Type of Work: Article | Post-print: After Peer Review
• Subjects: Health Sciences, Radiology; Chemistry, General; Chemistry, Nuclear
• Keywords: 99mTc tricarbonyl; lanthionine; 99mTc(CO)3(LAN); renal radiopharmaceuticals

Abstract

99mTc-mercaptoacetyltriglycine (99mTc-MAG3), 99mTc-dd- and ll-ethylene-di-cysteine (99mTc-EC) and 99mTc-mercaptoacetamide-ethylene-cysteine (99mTc-MAEC) contain N3S or N2S2 ligands designed to accommodate the four ligating sites of the {99mTcO}3+ core; they are all excellent renal imaging agents but have renal clearances less than that of 131I-orthoiodohippurate (131I-OIH). To explore the potential of the newly accessible but less polar {99mTc(CO)3}+ core having three ligating sites, we decided to build on the success of 99mTc-EC with its N2S2 ligand and two dangling carboxylates and have chosen an N2S ligand that also has two dangling carboxyls, lanthionine (LANH2), to form 99mTc(CO)3(LAN), a new renal radiopharmaceutical.Methods Biodistribution studies were performed on Sprague-Dawley rats by using 99mTc(CO)3(LAN) isomers, meso-LAN and dd,ll-LAN (an enantiomeric mixture), coinjected with 131I-OIH. Human studies were also performed by coinjecting each 99mTc product (~74 MBq [~2 mCi]) and 131I-OIH (~ 7.4 MBq [~ 0.2 mCi]) into 3 normal volunteers with dual-isotope imaging performed by using 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 a 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), respectively. At 3 hours, 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%), and red cell uptake was similar (24% and 21%) for 99mTc(CO)3(meso-LAN) and 99mTc(CO)3(dd,ll-LAN), respectively. Conclusion Although the plasma clearance and the rate of renal excretion of the 99mTc(CO)3(LAN) complexes are still less 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.