Pharmacokinetics and Imaging of²¹²Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients

Abstract

Purpose: Study distribution, pharmacokinetics, and safety of intraperitoneal (IP) 212 Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy. Experimental Design: IP 212 Pb-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/m 2 (7.4 MBq/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 7.67 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 212 Pb physical decay (T 1/2 = 10.6 hours). Follow-up >6 months showed no evidence of agent-related toxicity. Conclusions: Pharmacokinetics and imaging after 0.2 mCi/m 2 IP 212 Pb-TCMC-trastuzumab in patients with HER-2-expressing malignancy showed minimal distribution outside the peritoneal cavity, £ 6% urinary excretion, and good tolerance.

Absorbed Doses and Risk Estimates of 211At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

“…Phase I studies by our group [6] and Meredith et al [7,8] have shown its feasibility and safety in human subjects. However, because minimal residual disease is an infraclinical condition, some assumed already-cured patients should be considered part of the target group.…”

Safety and Outcome Measures of First-in-Human Intraperitoneal α Radioimmunotherapy With 212Pb-TCMC-Trastuzumab

“…The independent review shows more early patients with progression than previously noted when pretreatment and posttreatment comparison used the product of index lesion diameter (Table 2). 17,37 However, the later independent review did not necessarily use the same index lesions, which contributed to less than complete concordance of tumor growth results from those previously reported 17. Although the optimal tumor efficacy with α-emitters is proposed to be for microscopic disease, regression was noted among various sized gross lesions.…”

claMP Tag: A Versatile Inline Metal-Binding Platform Based on the Metal Abstraction Peptide

“…Radioactive tracer metals, such as 99m Tc, 55 Co, 64/67 Cu, or 212 Pb, also can be incorporated into the tag (manuscripts in preparation), and these isotopes have proven utility in diagnostic imaging. 48−54 As shown here, Ni(II) can be selectively inserted into the tag even when placed in a protein sequence, and though not currently in wide usage, 57 Ni could be substituted and monitored based on its positron or X-ray emission. 55,56 Ni- cla MP has been shown to act as catalytic antioxidant, 19−21 and the Ni- cla MP complex retains that activity in the context of a protein system.…”