The localization of human breast carcinomas by radiolabelled monoclonal antibodies

Abstract

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. Radioiodinated 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.