The localization of human breast carcinomas by radiolabelled monoclonal antibodies

Immune-deprived mice bearing HX99 human breast carcinoma xenografts were injected with a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to investigate the dependence of tumour localization on (i) tumour site and (ii) antibody radiolabel. No significant difference was found in the degree of localization of radio-iodinated M8 in subcutaneous, renal or intracranial xenografts, but a highly significant improvement in HX99 localization by M8 was recorded using an 111indium-DTPA conjugate of the antibody (111In-DTPA-M8), related to its rapid tumour uptake and blood pool clearance. Radio-iodinated or 111In-labelled M8 was given to 29 patients with breast cancer, 7 with primary tumours and 22 with metastases. Tumour localization was assessed by (i) examination of surgical specimens and (ii) antibody scans, which were compared with conventional X-rays and 99mTc-methylene diphosphonate (MDP) bone scans. Radiolabelled M8 localized preferentially in all primary tumours (radioactivity tumour: normal breast = 6.2 +/- 1.4 [mean +/- s.e.]). All ten patients with skeletal metastases had positive 111In-DTPA-M8 scans, but the correlation with X-rays and MDP scans showed a regional variation. Radio-iodinated M8 failed to identify metastases in any site. The favourable biodistribution of 111In-DTPA-M8 has led to the clear localization of breast carcinomas in patients and mice. In future such reagents may rationalize the clinical management of breast cancer.