CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Volume 29, Number 1, 2014
© Mary Ann Liebert, Inc.
Pharmacokinetics and Imaging of 212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients
AREVA Med: Eileen Banaga, Julien Torgue
UAB: Ruby F. Meredith, Michael T. Azure, Sui Shen, Souheil Saddekni, Ronda Carlise, Patty Bunch, Daniel Yoder, and Ronald Alvarez
Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy.
Experimental Design: IP 212Pb-TCMC-trastuzumab was delivered, after 4 mg/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 0.2 mCi/m2 (7.4MBq/m2) 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 6.3 nCi/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 7.67 mR/h and dropped to 0.67 mR/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 212Pb physical decay (T1/2 = 10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity.
Conclusions: Pharmacokinetics and imaging after 0.2 mCi/m2 IP 212Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, £ 6% urinary excretion, and good tolerance.