IMMUNOSCINTIGRAPHY OF SMALL-CELL LUNG-CANCER XENOGRAFTS WITH ANTI NEURAL CELL-ADHESION MOLECULE MONOCLONAL-ANTIBODY, 123C3 - IMPROVEMENT OFTUMOR UPTAKE BY INTERNALIZATION

The efficacy of three murine monoclonal antibodies (MAbs) for immunosc intigraphy of small-cell lung cancer (SCLC) xenografts was studied in a Balb/c nu/nu mouse model. These MAbs, 123C3, 123A8 and MOC191, belon g to cluster 1 of anti-SCLC MAbs and bind to the neural cell adhesion molecule (NCAM) with similar affinity. After intraperitoneal injection of these MAbs, labelled with I-125, the highest uptake in tumour tiss ue was obtained with MAb 123C3. Seven days after administration of thi s MAb 13.9% of the injected dose per gram of tumour tissue was retaine d in the tumour. The corresponding tumour to tissue ratios ranged from 3.97 for blood to 31.03 for colon. The imaging results and the tumour uptake were less favourable for the two other MAbs, 123A8 and MOC191 (fractions of injected dose respectively 6.7% and 9.2%), although affi nity, biological activity after labelling and uptake in non-tumour tis sues were very similar for all three MAbs. These results may be explai ned by the differences in the interaction between the MAbs and the tum our cells. MAb 123C3 is internalised into tumour cells, whereas both o ther anti-NCAM MAbs are not. Internalisation into NCI H69 cells was de monstrated in vitro by a radioimmunoassay, confocal laser scanning mic roscopy and electron microscopy. The internalised fraction of MAb 123C 3 was 22.3% after 24 h, whereas this fraction was only 7.5% for MAb 12 3A8. Although the internalised radiolabelled MAbs are usually degraded and dehalogenated intracellularly, the retained radioactivity is high . Apparently, intracellular degradation of radiolabelled MAb 123C3 and subsequent secretion of radioactive iodine did not prevent the accumu lation of intracellular radioactivity. In conclusion, accumulation and retention of radioactivity in the tumour tissue, due to internalisati on of radiolabelled MAbs, may improve the results of immunoscintigraph y.