Abstract

Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.