99mTc-MAEC complexes: new renal radiopharmaceuticals combining characteristics of (99m)Tc-MAG3 and (99m)Tc-EC

Abstract

99mTc-Mercaptoacetyltriglycine ((99m)Tc-MAG3) and (99m)Tc-L,L-ethylenedicysteine ((99m)Tc-LL-EC) are useful renal radiopharmaceuticals; however, both agents have renal clearances less than that of (131)I-orthoiodohippurate ((131)I-OIH), and (99m)Tc-LL-EC exists in dianionic and monoanionic forms at physiologic pH. In an effort to develop a superior (99m)Tc agent with a rapid clearance comparable with that of (131)I-OIH, we have designed a new ligand system, mercaptoacetamide-ethylene-cysteine (MAEC), which combines important structural features of both MAG3 and EC.

Methods: Biodistribution and clearance studies were performed on Sprague-Dawley rats using syn- and anti-(99m)Tc-L- and -D-MAEC coinjected with (131)I-OIH. Studies were also performed by coinjecting each isomer ( approximately 74 MBq [ approximately 2 mCi]) and 7.4-11.1 MBq (200-300 micro Ci) of (131)I-OIH in 3 volunteers with dual-isotope imaging performed 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: In the rats, <10% of the injected dose remained in the blood at 10 min after injection for all isomers, and the urine dose at 60 min ranged from 84% to 99% that of (131)I-OIH. The clearances of syn- and anti-(99m)Tc-L-MAEC in the rats were higher than the clearances for the D-isomers (P <or= 0.02) and were 102% and 105% that of (131)I-OIH, respectively. In humans, the plasma protein binding of the (99m)Tc-MAEC complexes ranged from 82% to 89%. All 4 complexes provided excellent renal images. The (99m)Tc-MAEC complex/(131)I-OIH plasma clearance ratio in humans ranged from 45% (anti-(99m)Tc-L-MAEC) to 74% (syn-(99m)Tc-D-MAEC) with the 180-min urine excretion equivalent to that of (131)I-OIH for all 4 complexes.

Conclusion: Initial data in humans suggest that syn-(99m)Tc-D-MAEC has a higher clearance than that of (99m)Tc-MAG3; however, none of the (99m)Tc-MAEC tracers have a clearance equivalent to that of (131)I-OIH and further ligand design is needed.