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

Abstract

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent ¹³¹I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targetting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of ¹³¹I-MIBG (110 MBq) and with ¹³¹I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with ¹³¹I-chCE7, the subcutaneous tumours nearly disappeared; treatment with ¹³¹I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour 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 cells, compared with a regrowth delay of 34 days with ¹³¹I-mAb chCE7 and of 24 days with ¹³¹I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by ¹³¹I-chCE7 compared with ¹³¹I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with ¹³¹I-MIBG and ¹³¹I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. ¹³¹I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate ¹³¹I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with ¹³¹I-MIBG.