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Localization and Imaging with Radioiodine-labeled Monoclonal Antibodies in a Xenogeneic Tumor Model for Human B-Cell Lymphoma¹

Department of Radiation Oncology [D. J. B., J. A. S., M. S. S., D. E. H., S. M. F.], and Department of International Medicine [P. A. F., S. L. W-M., J. E. J., K. A. F.], University of Michigan, Ann Arbor, Michigan 48109

Two MoAbs directed towards human B-cell malignancies have been studied in a preclinical animal model to evaluate their potential for in vivo imaging and therapy of B-cell lymphomas. Anti-B1 reacts with virtually all immunoglobulin-bearing malignancies and non-T acute lymphoblastic leukemia. Anti-J5 reacts with the common acute lymphoblastic leukemia antigen found on non-T acute lymphoblastic leukemia and follicular lymphomas. Anti-T1 which recognizes the CD5 antigen on most T-cell leukemias and lymphomas was used as a control antibody. These monoclonal antibodies were radiolabeled with ¹²⁵I or ¹³¹I by the ICI method. Namalwa (B-cell) and MOLT-4 (T-cell) tumors were grown s.c. in irradiated nude mice. The highest tissue concentration of ¹²⁵I-labeled anti-J5 in Namalwa-bearing mice was in blood and tumor. The tumor/blood ratio ranged from 0.7–1.2, with the highest ratio 4 days after injection. Pharmacokinetic analysis indicated that the t_1/2ß of anti-J5 from blood and other tissues ranged from 40–50 h, while the t_1/2ß for tumor averaged 65 h. The area under the curve of tumor was 2- to 5-fold higher than the area under the curve of liver, kidney, skin, and muscle. The peak tissue levels of ¹²⁵I-labeled anti-B1 in Namalwa-bearing mice were again in blood and tumor and 6 days following injection more than 5-fold greater activity was found in tumor compared to normal tissues other than blood. The tumor/blood ratio was 1.2 and 0.7 at 4 and 6 days after injection. ¹²⁵I-labeled anti-B1 showed minimal uptake in antigen-negative MOLT-4 tumors and ¹²⁵I-labeled anti-T1 showed little uptake in Namalwa tumors. Scintigraphic images were obtained following the injection of ¹³¹I-labeled anti-J5 and anti-B1 in nude mice bearing Namalwa tumors. These results indicate that radiolabeled anti-J5 and anti-B1 show promise as diagnostic and possibly therapeutic agents for human B-cell lymphoma, although there may be a limitation to clinical utility due to cross-reactivity with some normal cells.

¹ This investigation was supported by National Cancer Institute Grant CA43368 and a grant from the Dr. Louis Sklarow Memorial Fund, c/o Key Trust Co., 284 Main Street, Buffalo, NY 14202.

² To whom requests for reprints should be addressed, at Department of Radiation Oncology, University of Michigan, UH-Rm. B2C490/0010, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0010.

³ Present address: Roswell Park Memorial Institute, Division of Clinical Immunology, 666 Elm Street, Buffalo, NY 14263.

Received 9/16/87. Revised 1/21/88. Accepted 2/ 8/88.

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