Radioiodination of murine anti-alpha-foetoprotein E.9 monoclonal antibody and its F(ab')2 fragment for the diagnosis of hepatocellular carcinoma.
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.
Beyers
M
M
Atomic Energy Corporation of South Africa, Pretoria.
Aspinall
S
S
Conradie
J D
JD
Fourie
P J
PJ
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*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D000509:alpha-Fetoproteins