Breast cancer imaging with In-111 human IgM monoclonal antibodies: preliminary studies.

Abstract

Detection of specific tumor sites was studied with scintigraphy and radiolabeled human IgM monoclonal antibodies (MoAbs). Ten patients with metastatic breast cancer received an infusion of one of three indium-111-labeled anti-breast carcinoma MoAbs. The time of infusion ranged from 30 minutes to 2 hours. Three patients received YBB-190 at total doses of 2, 4.25, or 11 mg, four patients received YBM-209 at total doses of 1 mg (n = 1) or 20 mg (n = 3), and three patients each received 22 mg of YBY-088. Imaging was performed immediately after infusion and at 4, 24, 48, 72, 120, and 144 hours. Many presumed sites of metastatic disease were imaged in three of the four patients who received 20 mg of YBM-209 and in two of the three patients who received YBY-088. Tumor was not detected in any of the patients who received YBB-190, in the patient who received a 1-mg dose of YBM-209, or in the patient who received YBY-088 and in whom a biopsy of tumor tissue failed to demonstrate target antigen. The authors conclude that In-111-labeled human IgM MoAbs can target human breast cancer, but antigen expression and antibody dose determine successful immunoscintigraphy.

IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells

“…Potential disadvantages in using IgM mAb include the increased difficulty in purifying an IgM mAb compared to an IgG mAb and the theoretical problem that the large IgM mAb may have difficulty diffusing into extravascular areas. This latter issue has been examined in two recent imaging trials with radiolabeled human IgM mAb; positive tumor localization in patients with solid tumors was demonstrated [20,23]. There have been no reported clinical trials of mouse IgM in vivo for B cell neoplasms, but treatment of involved bone marrow ex vivo with cytotoxic murine IgM mAb and human complement can selectively lyse tumor cells without negatively affecting growth of normal bone marrow progenitor cells [22,24].…”

Chemical aspects of metal ion chelation in the synthesis and application antibody‐based radiotracers

“…Copper has a range of radionuclides with varying decay characteristics that are suitable for applications in both nuclear imaging and molecularly targeted radionuclide therapy. 16 Positron emission tomography imaging radionuclides of copper include 60 Cu (t 1/2 = 23.7 min), 61 Cu 62 Cu (t 1/2 = 9.67 min) but with the possible exception of 61 Cu for use in radiolabeling small peptides, proteins, and antibody-based fragments, the most suitable radionuclide for combination with immuno-PET is 64 Cu. 17 In addition to PET imaging, 64 Cu also shows potential for therapeutic applications via separate decay involving beta-particle emission.…”

Human monoclonal antibodies: A tool for cancer detection in vivo

“…Only a small fraction of the many clinical trials with anti-cancer antibodies have used human monoclonal antibodies , Haspel et al 1985, Ryan et al 1988, Steis et al 1990, Boven et al 1991, Ditzel et al 1993, Krause et al 1997. In the first in vivo tumor detection study in patients using human monoclonal antibodies, 1311-labeled anti-glioma antibody was used to localize a brain tumor .…”

“…In the first in vivo tumor detection study in patients using human monoclonal antibodies, 1311-labeled anti-glioma antibody was used to localize a brain tumor . In another study, 3 different "In-labeled human IgM antibodies were evaluated in 10 patients with metastatic breast cancer (Ryan et al 1988). One of the antibodies, YBM-209, successfully detected presumed sites in 3 of 3 patients.…”