A rat model system for radioimmunodetection of kappa myeloma antigen on malignant B cells

Abstract

A novel experimental model was established in normal rats for studying the localisation and tissue distribution of a murine monoclonal antibody directed against kappa light chain B cell malignancies. The antibody, K-1-21 was raised against human kappa Bence Jones Proteins and reacts with a cell membrane antigen KMA which is restricted to some kappa myeloma and lymphoma cells. In the rat model, kappa or lambda Bence Jones protein-conjugated sepharose was implanted subcutaneously on either flank 24 h before the injection of 131I-labelled K-1-21 or its F(ab')2 fragment. Gamma camera imaging and tissue distribution studies showed specific localisation of the K-1-21 antibody in the kappa sepharose. Injection of F(ab')2 antibody fragments resulted in faster background clearance, earlier delineation of the specific image and significantly higher target to blood ratios than those obtained with the intact antibody. These results suggest that the model may provide an alternative system to tumour xenograft bearing nude mice for studying localisation of antibodies with therapeutic potential.

An improved method for labeling monoclonal antibodies with samarium-153: use of the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid

“…Immunoreactivity of 153Sm-K-l-21. The immunoreactivity of the 163Sm-K-l-21 conjugates was assessed by a solid phase binding assay to immobilized LC Sepharose beads as previously described (1,12). HPLC Analysis of 153Sm-K-l-21.…”

“…Male Fisher 334 rats aged between 10 and 15 weeks were used for biodistribution studies, (test) and X (control) LC-conjugated Sepharose beads (ca. 0.5 mL) were implanted into opposite flanks of the animals as previously described (12). Twenty four hours after the placement of implants, groups of five animals were injected ip with 10-20 µg (0.3-1 MBq) of 153Sm-cDTPAa-K-l-21 or 153Sm-Mx-DTPA-K-l-21.…”

“…In this study we have investigated the suitability of Mx-DTPA as a bifunctional chelator for preparing 153Sm-mAb conjugates. In addition the biodistribution of 153Sm-Mx-DTPA-K-l-21 was compared with that of 153Sm-cDTPAa-K-l-21 in the antigen implant rat tumor model system (12). The number of chelator molecules per antibody molecule was determined with 14C intrinsically labeled Mx-DTPA (7).…”

Radio‐immunotargeting in experimental animal models of intraperitoneal cancer

“…into rats, being sequestered in the lung capillary bed (53). In a second model, antigen-coated Sepharose beads were implanted s.c. in rats (54).…”

Animal Models for Radiolabeled Monoclonal Antibodies in Cancer Research

“…Artificial targets (Table, section 111) with antigens bound to different types of particles can be used to study phenomena that are not related to the biology of the tumor (58,59). Exact quantitative studies can be done as the amount of antigen is known.…”