Pharmacokinetics and Imaging of 212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients

Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) Pb-212-TCMC-trastuzumab in patients with HER-2-expressing malignancy. Experimental Design: IP Pb-212-TCMC-trastuzumab was delivered, after 4mg/kg intravenous (IV) trastuzumab, to 3 patients with HER-2-expressing cancer who had failed standard therapies. Patients were monitored for toxicity and pharmacokinetics/dosimetry parameters. Results: Imaging studies after 0.2mCi/m(2) (7.4MBq/m(2)) show little redistribution out of the peritoneal cavity and no significant uptake in major organs. Peak blood level of the radiolabeled antibody, determined by decay corrected counts, was <23% injected dose at 63 hours; maximum blood radioactivity concentration was 6.3nCi/mL at 18 hours. Cumulative urinary excretion was 6% in 2.3 half-lives. The maximum external exposure rate immediately post-infusion at skin contact over the abdomen averaged 7.67mR/h and dropped to 0.67mR/h by 24 hours. The exposure rates at the other positions monitored (axilla, chest, and femur) decreased as a function of distance from the abdomen. The data points correlate closely with Pb-212 physical decay (T-1/2=10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity. Conclusions: Pharmacokinetics and imaging after 0.2mCi/m(2) IP Pb-212-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, 6% urinary excretion, and good tolerance.