Inhibition of the hepatocyte uptake of radiolabelled monoclonal antibodies by chelating agents |
| |
Authors: | B. R. Davidson P. B. Boulos J. B. Porter |
| |
Affiliation: | (1) Department of Surgery, University College and Middlesex School of Medicine, London, UK;(2) Department of Haematology, University College and Middlesex School of Medicine, London, UK;(3) Department of Surgery, Royal Free Hospital, Rowland Hill Street, NW3 2PF Hampstead, London, UK |
| |
Abstract: | The imaging of small abdominal tumours with indium 111 labelled monoclonal antibodies (MAbs) is often obscured by the uptake of activity into the hepto cytes of normal liver tissue. A model has therefore been developed to analyse reagents which may inhibit the he patocyte uptake of111In-MAb whilst preserving tumour uptake. Primary rat hepatocyte cultures and an epithelial membrane antigen (EMA) expressing tumour cell line (MCF7), recognised by the EMA-specific MAb ICR2, were obtained in tissue culture. Monolayers of both cells were incubated with the111In-MAb with or without the additional reagents and the cell uptake then measured and expressed per milligram of cell protein using a Lowry protein assay. No preferential reduction in hepatocyte uptake was noted by incubating cells with either saturated or unsaturated transferrin. The chelating agent, diethylene triamine penta-acetic acid (DTPA), however, significantly reduced the uptake of activity in hepatocytes but not the tumour cell line (TP<0.05). An optimum concentration and time period for incubating DTPA with labelled MAb was established. The mean hepatocyte uptake was reduced by 80% with a 1 h incubation with 1 mM DTPA. These results suggest that DTPA may have a role in reducing the liver uptake of radioactivity in patient studies using111In-MAb.This work was presented at the Society of Nuclear Medicine annual meeting, St. Louis, USA, July 1989 |
| |
Keywords: | Immunoscintigraphy Indium 111 Monoclonal antibody Chelating agents |
本文献已被 SpringerLink 等数据库收录! |
|