COMPARISON OF TECHNETIUM-99M-LL-EC ISOMERS IN RATS AND HUMANS

Technetium-99m-L,L-ethylenedicysteine (Tc-99m-LL-EC) is a new renal im aging agent with pharmacokinetic properties reported to be slightly su perior to those of Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3); howe ver, to better define the potential of the enantiomer Tc-99m-DD-EC and the diastereomer Tc-99m-DL-EC as renal imaging agents, we compared th e three EC stereoisomers with I-131-orthoiodohippurate (OIH) in a seri es of rats and humans. Methods: Each Tc-99m-EC stereoisomer was coinje cted with OIH in six Sprague-Dawley rats for measurements of clearance and extraction fraction. Each stereoisomer was also coinjected with O IH in three human volunteers followed by sequential imaging, plasma cl earance measurements and timed urine collections. Results: Technetium- 99m-DD-EC had the highest clearance and extraction efficiency in rats (p less than or equal to 0.02). In humans, image quality was good with all three agents. The clearance ratio (EC/OIH) was 82% +/- 8% for Tc- 99m-DD-EC compared to 70% +/- 3% and 40% +/- 5% for Tc-99m-LL-EC and T c-99m-DL-EC, respectively. Technetium-99m-DD and Tc-99m-LL-EC were exc reted more rapidly than Tc-99m-DL-EC. Conclusion: Technetium-99m-DD-EC has excellent imaging properties and the data suggest that its cleara nce may approach that of OIH more closely than any other Tc-99m renal agent. A potential limitation is the fact that both Tc-99m-DD and LL-E C exist in dianionic (80%) and monoanionic (20%) forms at physiologica l pH and it is unlikely that these two forms have the same clearance o r protein binding affinity.