Abstract

In a prospective study to assess the accuracy of monoclonal immunoscintigraphy for the detection of axillary lymph node metastases in breast cancer, two murine monoclonal antibodies that react with human breast cancer (3E1.2 and RCC-1) were labelled with 131iodine, and the radiolabelled antibody was injected subcutaneously into the interdigital spaces of both hands of 40 patients, 36 of whom had breast cancer and the remaining four of whom had fibroadenoma (the normal, contralateral axilla was used as a control). Of the patients with breast cancer, the findings from the scintigraphy images were correlated with histopathology or cytology of the axillary lymph nodes; images were regarded as positive and hence indicative of lymph node metastases if the amount of background-subtracted radioactive count in axilla on the side of breast cancer exceeded the contralateral normal side by a ratio greater than or equal to 1.5:1.0 as assessed by computer analysis. Using this method, immunoscintigraphy had an overall sensitivity of 33% (23% with 131I-3E1.2 and 50% with 131I-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with 131I-3E1.2 and 60% with 131I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with 131I-RCC-1 (IgG) were superior to 131I-3E1.2 (IgM) although the accuracy of immunoscintigraphy using 131I-RCC-1 (56%) was not much better than preoperative clinical assessment (50%). However, there were cases when immunoscintigraphy using radiolabelled antibody (IgM or IgG) detected axillary lymph node metastases not suspected by clinical examination. Thus it appears that while immunoscintigraphy may be a useful adjunct to preoperative clinical assessment and is simple and safe, a major improvement in its accuracy is needed before it can replace axillary dissection and histological examination in the accurate staging of axilla in breast cancer.

Highlights

  • The detection of overt tumour deposits by means of gammacamera imaging and radiolabelled monoclonal antibodies to tumour-associated antigens has met with encouraging results (Armitage et al, 1984; Epenetos, 1985; Leyden et al, 1986; Mach et al, 1981; Rainsbury, 1984; Smedley et al, 1983; William et al, 1984)

  • Antibody administration was well tolerated by all the patients with no adverse reactions occurring except for the development of human anti-mouse antibody response at 4 weeks after injection in 2/24 patients, one of whom had 1311-3E1.2 and the other 131I-RCC-l

  • Correct prediction of the axillary lymph node status was obtained in 41% (9/22) of the patients by the preoperative scans and in 59% (13/22) of the patients by preoperative clinical assessment (Table II)

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Summary

Introduction

The detection of overt tumour deposits by means of gammacamera imaging and radiolabelled monoclonal antibodies to tumour-associated antigens (immunoscintigraphy) has met with encouraging results (Armitage et al, 1984; Epenetos, 1985; Leyden et al, 1986; Mach et al, 1981; Rainsbury, 1984; Smedley et al, 1983; William et al, 1984). Most of these studies have been performed on patients with well documented and widespread disease; few being prospective studies of the value of monoclonal immunoscintigraphy in the initial staging of patients with malignant disease. Dehalogenation of radiolabelled antibody, poor penetration of the conjugate into tumour deposits and antibody binding to cross-reactive antigens present on normal cells are further limitations to successful antibody targetting and of immunoscintigraphy (Bradwell et al, 1985; Rockoff et al, 1980)

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