Improved Delivery of Radiolabeled Anti-Bl Monoclonal Antibody to Raji Lymphoma Xenografts by Predosing with Unlabeled Anti-Bl Monoclonal Antibody

Academic Article

Abstract

  • A human B-cell lymphoma xenograft model was used to test whether the administration of unlabeled MoAb prior to injection of radiolabeled monoclonal antibody (MoAb) improves delivery of the radiolabeled MoAb to tumor prior to testing in clinical radioimmunotherapy trials. The anti-Bl/CD20 pan-B-cell MoAb reactive with human B-cell lymphomas and leukemias but not reactive with mouse B-cells was used in this study. Athymic nude mice bearing human Raji Burkitt lymphoma xenografts were given injections of 2.5 pCi (03 Mg) 13lI-labeled anti-Bl with or without a 2-h prior single injection of 100 Mg of unlabeled anti-Bl antibody. Four days later the animals given injections of 131I-labeled anti-Bl and the unlabeled anti-Bl predose had a tumor uptake of 12.72 ± 1.17% (SEM) of injected dose/g which was 44% greater than the animals receiving the 13lI-labeled anti-Bl alone (P = 0.014). The uptake in most normal tissues was unchanged, although the blood level of l31I-labeled anti-Bl appeared to be greater following unlabeled anti-Bl predosing (P = 0.067). Predosing with isotype matched irrelevant MoAb did not result in a greater tumor uptake or blood concentration of l3iI-labeled anti-Bl compared to the administration of 13lI-labeled anti-Bl alone. In studies using11′In-labeled anti-Bl, the effect of unlabeled antibody predosing was more pronounced. For animals given injections of 4.5 MCi (0.4 Mg) 11′In-labeled anti-Bl and the unlabeled anti-Bl predose, the uptake in tumor was 1237 ± 2.07% of injected dose/g which was 162% greater than the animals receiving the 1 “In-labeled anti-Bl alone (P = 0.009). Predosing decreased 11′In-labeled anti-Bl uptake in spleen, while the blood level was significantly greater. Predosing was more effective than simultaneous injection in improving tumor delivery. When tumor-bearing mice were either simultaneously given injections of 56 Mg of unlabeled anti-Bl and 4 Mg “‘In-labeled anti-Bl or were given preinjections of 36 Mg unlabeled anti-Bl 3 h prior to injection of 4 Mg 11′In-labeled anti-Bl, tumor uptake 3 days later was 13-fold higher in the animals which received the preinjection of unlabeled antibody (P = 0.011). As the quantity of unlabeled anti-Bl was increased (36,96,996 Mg) in the predose, significantly greater uptake in tumor was observed, although this uptake appeared to plateau at the highest pre-doses. This was accompanied by an increase in 11′In-labeled anti-Bl in blood and a decrease in uptake in the spleen. It thus appears that unlabeled pan-B-cell MoAb predosing results in superior targeting of subsequently administered radiolabeled anti-Bl MoAb to tumor. Since it is unlikely that free antigen or tumor cells are present in the circulation in this animal model, it appears that blocking of specific anti-Bl Fc receptor sites by unlabeled anti-Bl predosing is involved in the enhanced tumor uptake. These results may have significant impact on the way in which radiolabeled pan-B-cell MoAbs should be delivered in clinical trials. © 1992, American Association for Cancer Research. All rights reserved.
  • Published In

  • Cancer Research  Journal
  • Author List

  • Buchsbaum DJ; Kaminski MS
  • Start Page

  • 637
  • End Page

  • 642
  • Volume

  • 52
  • Issue

  • 3