NEW RENAL-FUNCTION IMAGING AGENTS .1. SYNTHESIS AND BIOLOGICAL CHARACTERIZATION OF A [TC-99M]DIAMINOMERCAPTO(THIO)ETHER (DAMTE)

The present study describes the synthesis of a [Tc-99m]diaminomercapto (thio)ether (DAMTE-derivative) as a first compound of a new class of T c-99m-complexes which is tubular excreted. -Benzoyl-8-keto-7-aza-2-ami no-4,10-dithia-decanoic acid (CO2-DAMTE 3) was synthesized by the reac tion of succinimidyl-S-benzoyl-thioglycolate and (S)-2-aminoethyl-L-cy steine. The respective tech netium complex, Tc-99m-CO2-DAMTE was obtai ned in radiochemical yields of about 70% using stannous chloride as re ducing agent. Hydrolysis of the protecting group was performed either prior to the complexation of pertechnetate (''cold kit'') or during th e labelling reaction (''hot kit''). Organ distribution was determined in Wistar rats. Within 24 h 40% of the activity were excreted into the feces and 43% into the urine, whereas 10% were retained in the kidney s. In contrast, a first human study showed a very fast renal eliminati on of Tc-99m-CO2-DAMTE, a low liver uptake (<10%) and no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m(2) in ad dition to the protein binding of >95% suggests an effective tubular ex cretion of the compound.