A comparison of targetting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model andimaging of neuroblastoma patients

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the ef fective neuroblastoma-seeking agent I-131-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice wi th neuroblastoma xenografts and (b) its tumour targetting ability in neurob lastoma patients. The SK-N-SH tumour cells used in the mouse experiments sh ow good MIBG uptake and provide a relatively low number of 6,300 binding si tes/cell for mAb chCE7. Tumours were treated with single injections of I-13 1-MIBG (110 MBq) and with I-131-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with I-131-chCE7, the subcutaneo us tumours nearly disappeared; treatment with I-131-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumo ur regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cell s, compared with a regrowth delay of 34 days with I-131-mAb chCE7 and of 24 days with I-131-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the tr eatments. The superior growth inhibition achieved by I-131-chCE7 compared w ith I-131-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chC E7 with LI-CAM present in normal human tissues was investigated by direct b inding of radioiodinated mAb to frozen tissue sections. Results showed a st rong reaction with normal human brain tissue and weak but detectable bindin g to normal adult kidney sections. Seven patients with recurrent neuroblast oma were sequentially imaged with I-131-MIBG and I-131-chCE7. The results u nderlined the heterogeneity of neuroblastoma and showed the two imaging mod alities to be complementary. I-131-ChCE7 scintigraphy may have clinical uti lity in detecting metastases which do not accumulate I-131-MIBG, and the an tibody may hold potential for radioimmunotherapy, either by itself or in co mbination with I-131-MIBG.