THE SAFETY AND PHARMACOKINETICS IN ADULT SUBJECTS OF AN INTRAVENOUSLYADMINISTERED TC-99M-LABELED 17 AMINO-ACID PEPTIDE (CYT-379)

A phase I study was designed to evaluate the safety and pharmacokineti cs of a novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCT CCA-amide (CYT-379), which binds to the fibrinogen receptor of activat ed platelets and also binds to Tc-99m. Eleven subjects with suspected deep venous thrombosis had 0.1, 0.5 or 1.0 mg of the peptide infused i ntravenously. Pharmacokinetics were determined by assaying blood sampl es in 6 of the 11 subjects and by urine sampling in 5 of these 6 subje cts. Plasma and whole blood time-activity curves demonstrated an initi al fast component with half-time clearance of 0.2 +/- 0.01 and 0.2 +/- 0.02 h and a slow component with half-time clearance of 2.8 +/- 0.3 a nd 2.7 +/- 0.2 h (mean +/- SEM for plasma and whole blood, respectivel y). Urine clearance was 22.6 +/- 3.3 and 10.8 +/- 1.6 mL/min when norm alized to body surface area. The cumulative excretion of Tc-99m-CYT-37 9 in the urine was 16.6 +/- 3.6, 45.6 +/- 16.9 and 45.6 +/- 1.8% of th e administered dose over 0-2, 0-12 and 0-24 h after radiopharmaceutica l injection, respectively. Images obtained in 11 subjects immediately, at 1-2, and 4-6 h after injection were evaluated for abnormalities an d were compared with duplex Doppler ultrasonography. Tc-99m-CYT-379 im ages were positive in only 3 of 7 subjects who had a positive duplex D oppler examination in at least one lower extremity. One subject with n egative duplex Doppler had also negative Tc-99m-CYT-379 scintigraphy. One subject with negative scintigraphy and two other subjects with pos itive scintigraphy had no other imaging studies of the deep venous sys tem performed. No adverse reactions were observed during or after the infusion of Tc-99m-CYT-379. Tc-99m-CYT-379 appears to be a safe radiop harmaceutical and demonstrates rapid clearance from plasma in human su bjects.