Detection of colorectal carcinoma by emission-computerized tomography after injection of 123I-labeled Fab or F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen antibodies.

Abstract

This clinical study was based on experimental results obtained in nude mice grafted with human colon carcinoma, showing that injected 131I-labeled F(ab)2 and Fab fragments from high affinity anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAb) gave markedly higher ratios of tumor to normal tissue localization than intact MAb. 31 patients with known colorectal carcinoma, including 10 primary tumors, 13 local tumor recurrences, and 21 metastatic involvements, were injected with '13I-labeled F(ab')2 (a = 14) or Fab (a = 17) fragments from MAb anti-CEA. The patients were examined by emission-computerized tomography (ECT) at 6, 24, and sometimes 48 h after injection using a rotating dual head scintillation camera. All 23 primary tumors and local recurrences except one were clearly visualized on at least two sections of different tomographic planes. Interestingly, nine of these patients had almost normal circulating CEA levels, and three of the visualized tumors weighed only 3-5 g. Among 19 known metastatic tumor involvements, 14 were correctly localized by ECT. Two additional liver and several bone metastases were discovered by immunoscintiraphy. Altogether, 86% of the tumor sites were detected, 82% with F(ab')2 and 89% with Fab fragments. The contrast of the tumor images obtained with Fab fragments suggests that this improved method of immunoscintigraphy has the potential to detect early tumor recurrences and thus to increase the survival of patients. The results of this retrospective study, however, should be confirmed in a prospective study before this method can be recommended for the routine diagnosis of cancer.

Secretion of functional antibody and Fab fragment from yeast cells.

“…Of the latter two groups, antibody molecules or the protein fragments that contain their antigen-binding domains, Fab and F(ab')2 ( Fig. 1), are particularly important for a wide variety of applications, including detection and treatment of human disease (8,9), in vitro diagnostic tests (10), and affinity purification methods (11). Chimeric antibodies that consist of mouse variable (V) regions fused to human constant (C) regions may be especially valuable for human therapeutic or in vivo diagnostic uses, since they are potentially less immunogenic in humans than are mouse antibodies.…”

N-glycosylation and microtubule integrity are involved in apical targeting of prostate-specific membrane antigen: implications for immunotherapy

“…The altered localization of carcinoembryonic antigen allows accessibility of this antigen to the underlying vasculature and would explain why immunoscintigraphic studies using i.v. injected mAbs to carcinoembryonic antigen are able to specifically label primary and metastatic tumors but not normal or well-differentiated tissues (49,50).…”

Pilot Trial Evaluating an 123I-Labeled 80-Kilodalton Engineered Anticarcinoembryonic Antigen Antibody Fragment (cT84.66 Minibody) in Patients with Colorectal Cancer

“…123 I-labeled antibody fragments to human milk fat globule (50) and CEA (47,48) Lower-molecular-mass antibody fragments have much faster clearance rates than intact antibodies, which increases tumor-to-blood ratios, reduces background activity, and makes them attractive as potential tumor-imaging agents. However, peak uptake and retention times in tumors are often reduced.…”