This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adams, G. P. Articles by Epstein, A. L. Search for Related Content PubMed PubMed Citation Articles by Adams, G. P. Articles by Epstein, A. L.

Effect of Mass of ¹¹¹In-Benzyl-EDTA Monoclonal Antibody on Hepatic Uptake and Processing in Mice¹

Departments of Internal Medicine, Section of Radiodiagnosis and Therapy, University of California Davis Medical Center, Sacramento 95817 [G. P. A., S. J. D., S. V. D., G. L. D.]; Department of Chemistry, University of California, Davis 95616 [C. F. M., M. J. M.]; and Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033 [A. L. E.], California

In patients, the pharmacokinetic behavior of murine monoclonal anti-bodies has been observed to vary with the amount of antibody administered. It has been suggested that this reflects human recognition of the foreign mouse protein. We have found that the amount of antibody administered also influenced pharmacokinetic behavior when murine monoclonal antibody was administered to mice.

p-Isothiocyanatobenzyl-EDTA, a new chelator which forms complexes with ¹¹¹In that are stable in vivo, was conjugated to Lym-1, a murine anti-Burkitt's lymphoma monoclonal antibody. The pharmacokinetics of two doses (20 and 0.2 µg) of the ¹¹¹In labeled radiopharmaceutical were studied in non-tumor bearing BALB/c mice. About 20% (0.04 µg) of the 0.2-µg dose, compared with 8% (1.6 µg) of the 20-µg dose, was found in the liver at 48 h after injection. Both doses demonstrated a biological half-life of approximately 120 h. At least 75% of the ¹¹¹In was excreted by the kidneys, and essentially all ¹¹¹In in the urine remained chelated by the EDTA portion of p-isothiocyanatobenzyl-EDTA. From these observations of a dose dependent uptake of this radiopharmaceutical by the liver we conclude that there is a recognition phenomenon in mice for this murine monoclonal antibody.

¹ This work was supported by Department of Energy Grant DE FG03-84ER60233 (S. J. D.) and National Cancer Institute Grant CA16861 (C. F. M.).

² To whom requests for reprints should be addressed, at Division of Radiodiagnosis and Therapy, University of California Davis Medical Center, FOLB 2E, 4301 X St., Sacramento, CA 95817.

Received 4/20/88. Revised 10/ 3/88. Revised 1/ 5/89. Accepted 1/ 9/89.

This article has been cited by other articles:

				G. P. Adams, C. C. Shaller, E. Dadachova, H. H. Simmons, E. M. Horak, A. Tesfaye, A. J. P. Klein-Szanto, J. D. Marks, M. W. Brechbiel, and L. M. Weiner A Single Treatment of Yttrium-90-labeled CHX-A''-C6.5 Diabody Inhibits the Growth of Established Human Tumor Xenografts in Immunodeficient Mice Cancer Res., September 1, 2004; 64(17): 6200 - 6206. [Abstract] [Full Text] [PDF]

				G. L. DeNardo, S. J. DeNardo, D. L. Kukis, R. T. O'Donnell, S. Shen, G. R. Mirick, and C. F. Meares Metabolite Production in Patients with Lymphoma After Radiometal-Labeled Antibody Administration J. Nucl. Med., September 1, 2001; 42(9): 1324 - 1333. [Abstract] [Full Text] [PDF]

				X B Shi, P H Gumerlock, A A Wellman, C F Meares, G L DeNardo, F J Meyers, and S J DeNardo Rapid PCR construction of a gene containing Lym-1 antibody variable regions. Genome Res., August 1, 1993; 3(1): 46 - 53. [PDF]