Clinical pharmacology, metabolism, and tissue distribution of⁹⁰ y-labeled monoclonal antibody B72.3 after intraperitoneal administration

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi ⁹⁰Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total ⁹⁰Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 ± 4.5 hours. A low-molecular-weight ⁹⁰Y-labeled species of metabolite was identified by high-performance liquid chromatog-raphy. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the ⁹⁰Y-labeled metabolite and the ⁹⁰Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 ± 2.2 hours and 25 ± 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 ± 3 hours for the metabolite and 42 ± 17 hours for B72.3. Approximately 8%-ll% of the total injected ⁹⁰Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the Y-labeled metabolite, but about 30% of the ⁹⁰Y label in urine appeared identical to the authentic Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of ⁹⁰Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of ⁹⁰Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the ⁹⁰Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of ⁹⁰Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of ⁹⁰Y administered. Thus, if an adequate total radiation dose can be achieved, ⁹⁰Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease. [J Natl Cancer Inst 83:1629-1636,1991]