Biokinetics of yttrium-90–labeled huBrE-3 monoclonal antibody
Version of Record online: 12 FEB 2002
Copyright © 2002 American Cancer Society
Supplement: Eighth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer
Volume 94, Issue Supplement 4, pages 1240–1248, 15 February 2002
How to Cite
Johnson, T. K., Cole, W., Quaife, R. A., Lear, J. L., Ceriani, R. L., Jones, R. B. and Cagnoni, P. J. (2002), Biokinetics of yttrium-90–labeled huBrE-3 monoclonal antibody. Cancer, 94: 1240–1248. doi: 10.1002/cncr.10292
- Issue online: 12 FEB 2002
- Version of Record online: 12 FEB 2002
- Manuscript Accepted: 14 NOV 2001
- Manuscript Received: 31 OCT 2001
- NIH. Grant Numbers: ROI-CA62352, ROI-CA61532
- huBrE-3 antibody;
- breast cancer;
This study reports summary biokinetics for 17 patients treated with huBrE-3 antibody labeled with indium-111 (111In) and yttrium-90 (90Y) in a Phase I dose escalation trial.
Patients were infused with huBrE-3 antibody conjugated to 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyl-diethylenetriamine pentaacetic acid (MX-DTPA). The huBrE-3 was labeled with increasing amounts of 90Y radioactivity according to the following activity regimen: 10 mCi/m2, 20 mCi/m2, 33 mCi/m2, 50 mCi/m2, and 70 mCi/m2. In addition to the 90Y activity, 3–5 mCi of 111In was labeled to huBrE-3 to serve as an imaging agent. In characterizing the biokinetics of huBrE-3, serial urine and blood samples were acquired. Additionally, whole-body imaging using a scintillation camera was performed at four time points postinfusion.
Cumulative urine data yielded a plot of total-body biologic excretion that was relatively flat. Total body regions of interest derived from nuclear medicine scintigrams decreased according to a monoexponential function with a slope slightly greater than the rate of physical decay. When physical decay was combined with the urine biologic excretion rate, the calculated rate of activity decrease was indistinguishable from the scintigraphic rate of decrease in total-body activity.
The authors concluded from these observations that the radioactivity remains essentially inside the patient, that biologic excretion of activity from the total body is not appreciable, and that the path for biologic excretion of activity that does occur is via the urine. The half-time associated with the β (slow) phase for extraction from the blood averages 40.5 hours. Since large amounts of radioactivity do not appear in the urine, and total-body activity is decreased approximately according to physical decay (64.1 hours), activity must pool elsewhere after leaving the blood. The logical place is the skeleton, with possible selective binding to the bone marrow. Bone marrow biopsies from 4 of 7 patients who consented to serial biopsies were supportive of this conclusion. Cancer 2002;94:1240–8. © 2002 American Cancer Society.