New renal function imaging agents. I. Synthesis and biological characterization of a...

The present study describes the synthesis of a [99mTc]diaminomercapto(thio)ether (DAMTE-derivative) as a first compound of a new class of 99mTc-complexes which is tubular excreted. 10-Benzoyl-8-keto-7-aza-2-amino-4,10-dithia-decanoic acid (CO2-DAMTE 3) was synthesized by the reaction of succinimidyl-S-benzoyl-thioglycolate and (S)-2-aminoethyl-L-cysteine. The respective technetium complex, 99mTc-CO2-DAMTE was obtained in radiochemical yields of about 70% using stannous chloride as reducing agent. Hydrolysis of the protecting group was performed either prior to the complexation of pertechnetate ("cold kit") or during the 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 kidneys. In contrast, a first human study showed a very fast renal elimination of 99mTc-CO2-DAMTE, a low liver uptake (< 10%) and no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m2 in addition to the protein binding of > 95% suggests an effective tubular excretion of the compound.