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 Beatty, B. G. Articles by O'Connor-Tressel, M. Search for Related Content PubMed PubMed Citation Articles by Beatty, B. G. Articles by O'Connor-Tressel, M.

Effect of Specific Antibody Pretreatment on Liver Uptake of ¹¹¹In-labeled Anticarcinoembryonic Antigen Monoclonal Antibody in Nude Mice Bearing Human Colon Cancer Xenografts¹

Department of General Oncologic Surgery [B. G. B., J. D. B., M. O-T.] and the Division of Radiologic Sciences [L. E. W.], City of Hope National Medical Center, and the Division of Immunology [R. J. P., J. E. S.], Beckman Research Institute of the City of Hope, Duarte, California 91010

Administration of a large dose (0.2 mg) of unlabeled specific anticarcinoembryonic antigen (anti-CEA) monoclonal antibody (MAB) to nude mice bearing LS174T human colon cancer xenografts significantly decreased normal liver uptake of ¹¹¹In-labeled anti-CEA MAB (Indacea). Mice bearing tumors of approximately 1 g showed liver accumulation of indium-111 at 48 h following injection of 2 µg/10 µCi Indacea of 33.8 ± 1.5% injected dose per gram (%ID/g) (N = 25). Treatment with 0.2 mg unlabeled anti-CEA MAB reduced this to 8.9 ± 0.5% ID/g (N = 22; P < 0.001). The dose of pretreatment was found to be critical. Increasing the amount of unlabeled MAB to 2.0 mg did not significantly improve the liver level of indium-111, but did compromise the tumor uptake of Indacea (15.9 ± 1.3 versus 12.4 ± 0.4 %ID/g; P < 0.05). Lowering the dose of pretreatment 10-fold resulted in increased (P < 0.001) liver uptake of the label (26.5 ± 2.8 %ID/g). The unlabeled anti-CEA MAB treatment given as a single dose or fractionated over several days gave the same results. The decrease in liver uptake was the same for i.v. administration of the unlabeled MAB given 1 week prior to Indacea injection or mixed together with Indacea. With i.p. administration, simultaneous injection of the unlabeled MAB with Indacea was not as effective as pretreatment (20 min to 7 days) in decreasing the liver uptake of ¹¹¹In (P < 0.05). Epitope specificity and affinity were shown to be important considerations in the choice of MAB combinations used for pretreatment and imaging. Pretreatment with nonspecific MAB was ineffective in decreasing liver uptake of Indacea.

¹ Work supported in part by grants from NIH Biomedical Research Support Grant (RR 05471), NCI Grants (CA 33572 and CA 43904), and Medi-Physics Inc., Emeryville, CA.

² Address for correspondence: Barbara G. Beatty, Ph.D., City of Hope National Medical Center, Department of General Oncologic Surgery, 1500 East Duarte Road, Duarte, CA 91010.

Received 6/ 1/88. Revised 10/31/88. Accepted 12/19/88.

This article has been cited by other articles:

				V. Kenanova, T. Olafsen, L. E. Williams, N. H. Ruel, J. Longmate, P. J. Yazaki, J. E. Shively, D. Colcher, A. A. Raubitschek, and A. M. Wu Radioiodinated versus Radiometal-Labeled Anti-Carcinoembryonic Antigen Single-Chain Fv-Fc Antibody Fragments: Optimal Pharmacokinetics for Therapy Cancer Res., January 15, 2007; 67(2): 718 - 726. [Abstract] [Full Text] [PDF]