title: Radioiodination of murine anti-alpha-foetoprotein E.9 monoclonal antibody and its F(ab')2 fragment for the diagnosis of hepatocellular carcinoma.
abstract: The high incidence of hepatocellular carcinoma amongst certain population groups of Southern Africa made feasible the investigation of a radiolabelled monoclonal anti-alpha-foetoprotein as a radioimmunodiagnostic agent for this disease. This paper reports the preclinical trials with monoclonal anti-alpha-foetoprotein E.9 (anti-AFP) and its F(ab')2 fragment after radiolabelling with 131I. Various radioiodinations were tried. The best results were obtained with the lodogen and Bolton-Hunter methods. 131I from only one of the sources tested gave an 131I-labelled anti-AFP with meaningful immunoreactivity. It was shown by means of gamma-camera scans and monitoring of radioactivity in individual organs that 131I-anti-AFP and the 131I-anti-AFP F(ab')2 fragments did not accumulate abnormally in any organ(s) in healthy animals. The correlation in healthy mice of the biodistribution of 125I human IgG to 131I-anti-AFP, and 125I human IgG to 131I-F(ab')2 was good. Human hepatoma xenografts in athymic mice showed uptake of 131I-anti-AFP and the 131I-F(ab')2 fragment. The uptake of 131I-F(ab')2 was improved by liver background subtraction. There was correlation between circulatory alpha-foetoprotein concentrations and tumour uptake of 131I-F(ab')2 in tumour-bearing athymic mice and a definite relationship was found between tumour size and radiolabelled antibody and the F(ab')2 fragment. After the biological action of the 131I-anti-AFP and the 131I-F(ab')2 fragment was known, sterile pyrogen-free consignments were supplied for clinical trials in humans on a regular basis.
authors: Atomic Energy Corporation of South Africa, Pretoria.
authors: M
authors: M
authors: Beyers
authors: S
authors: S
authors: Aspinall
authors: J D
authors: JD
authors: Conradie
authors: P J
authors: PJ
authors: Fourie
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011817:Rabbits; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins