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

摘要

^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.MethodsBiodistribution 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.