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 Y-90. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total Y-90 label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight Y-90-labeled species of metabolite was identified by high-performance liquid chromatography. 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 Y-90-labeled metabolite and the Y-90-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%-11% of the total injected Y-90 label appeared in urine over 72 hours. Most of the label (about 70%) was present as the Y-90-labeled metabolite, but about 30% of the Y-90-label in urine appeared identical to the authentic Y-90-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of Y-90 (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 Y-90 were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the Y-90 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 Y-90 label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of Y-90 administered. Thus, if an adequate total radiation dose can be achieved, Y-90-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.
