Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous xenograft model of neuroblastoma in SCID mice

PURPOSE: To evaluate a novel strategy of immunolocalization of human neuroblastoma by targeting the neural cell adhesion molecule (NCAM), which is over-expressed on neuroblastoma.

METHODS: NCAM expression on the cell surface of established neuroblastoma cells was shown by flow cytometry. A SCID mouse model using IMR5-75 neuroblastoma cells to induce subcutaneous tumour growth was established. 131I was used to label monoclonal NCAM specific ERIC1 antibodies generating the 131I-ERIC1 antibody, which showed a high affinity to NCAM also after labelling (KD=9 x 10(-8) mol . l(-1)).

RESULTS: Measurement of organ-specific radioactivity showed low organ-specific uptake (5.33%ID/g (percent of injected dose per gram of tissue) after 72 h), which continuously decreased over the 96 h investigation period, demonstrating clearance of radioactivity. In contrast, tumours accumulated radioactivity continuously up to a peak of 42.07%ID/g at the 96 h time point (31.07%ID/g at 72 h). This specific uptake could be blocked by application of unlabelled ERIC1 antibodies. Measurement of blood specific radioactivity revealed a characteristic clearance over the first 72 h. With 37 Gy, tumour-specific radioactivity reached therapeutic doses after 96 h.

CONCLUSIONS: These results indicate that 131I-labelled ERIC1 has the ability to probe NCAM-expressing tumour cells in vivo with high efficiency and is a promising reagent for the diagnosis and treatment of NCAM-positive human tumours, especially for neuroblastoma.