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. 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.

The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody

“…With antibodies labelled with charged metallic ions such as Indium-111 ["'In] using a chelating agent (usually diethylene triamine pentacetic acid (DTPA)), unstable non specific protein binding may be a major factor in the background uptake of radioactivity (Hnatowich & McGann, 1987). This problem is most evident with the liver which may accumulate 30-40% of the injected radioactivity (Rainsbury, 1984). The pretreatment of "'In labelled antibodies with metal chelating agents has been shown in tissue culture to reduce the uptake of radioactivity by hepatocytes and may, therefore, improve the results of immunoscintigraphy (Davidson et al, 1990).…”

Kinetics, quantitative analysis and radioimmunolocalization using indium-111-HMFG1 monoclonal antibody in patients with breast cancer

“…Several investigators have reported successful radioimmunolocalisation of breast cancer (Colcher et al, 1983;Rainsbury, 1984;Kalofonos et al, 1988b), but limitations of this approach are the low absolute amount of antibody reaching the target (Epenetos et al, 1986), the heterogeneity of antigenic expression in tumour cells affecting antibody binding (Buchegger et al, 1983) and the persistence of high levels of blood pool radioactivity which makes tumour radioimmunodetection difficult. Several methods have been reported to reduce the blood pool activity.…”

Localisation of gastrointestinal cancer with a 131 I labelled monoclonal antibody to CEA

“…The amount accumulated, however, is so low that detectable contrast from normal tissues cannot be reliably achieved by external scanning. Attempts to increase the tumour to normal tissue contrast have evaluated different isotopes (Fairweather et al, 1983b;Rainsbury, 1984) and different methods of scanning such as emission tomography (Berche et al, 1982). These techniques, however, are methods of improving the sensitivity of the detection of the very small amounts of labelled antibody accumulated by tumours.…”