The detection of axillary lymph node metastases from breast cancer by radiolabelled monoclonal antibodies: a prospective study

Abstract

Summary 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 13'iodine, 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 ) 1.5:1.0 as assessed by computer analysis. Using this method, immunoscintigraphy had an overall sensitivity of 33% (23% with 1311-3E1.2 and 50% with 1311-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with 1311-3E1.2 and 60% with 131I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with 1311-RCC-1 (IgG) were superior to 1311-3E1.2 (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.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). However, 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. Immunoscintigraphy is complicated in that imaging using intravenously administered radiolabelled antibodies has a considerable background radioactivity because of the uptake of radiolabelled material in the blood pool and extravascular spaces, and antibodies may be catabolised before reaching their target, resulting in only a very small tumour uptake. In addition, dehalogenation of radiolabelled antibody, poor penetration of the conjugate into tumour deposits and antibody binding to cross-reactive antigens present on normal cells are...

Expression and distribution of N‐acetyl and N‐glycolylneuraminic acids in secreted and cell‐associated glycoconjugates by two human osteosarcoma cell lines

“…Neu5Ac is present in the majority of sialic acid-containing tumor markers in humans, even though emerging data suggests that Neu5Gc is also correlated with certain human cancers (Kawai, 1991;Tzanakakis et al, 2006). The Neu5Gc constitute an epitope for the HanganutziuDeicher antibodies whose levels may be elevated in the sera of certain cancer patients and may be of prognostic or diagnostic value (Tjandra et al, 1989). Furthermore, studies with mice bearing tumors induced by F3II mammary carcinoma and B16 melanoma cells, which possess Neu5Gc-containing epitopes, showed that administration of specific antibodies against these epitopes caused a reduction in tumor size (Vazques et al, 2000).…”

Development of human anti‐murine antibody (HAMA) response in patients

“…The purified Ly2-1 antibody was labelled with non-radioactive sodium iodide or '^'l using the chloramine T method (26). Preparation of the iodinated antibodies has been previously described (3,21).…”

“…Irrelevant murine MoAb used to evaluate the HAMA response included BCl (IgGi), BC2 (igGl), and BC3 (IgM) which were directed against mucin-like glycoproteins of breast (20); and polyclonal antibodies of monkey and sheep origin (produced in our laboratory). MoAb 3E1 2 was purified from ascitic fluid (21) and the antibodies RCC-1 and Ly-21 were purified on Protein A-Sepharose (Pharmacia inc., Piscataway, New Jersey, USA as described previously (22); antibodies 30-6,1-1 and JGT by Protein A-Suparose (Pharmacia Inc., Piscataway, NJ). Purity was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.…”

Determination of Metastatic Axillary Lymph Node in Breast Cancer: Differentiation with Dynamic MRI Examination by Signal Intensity-Time Curves

“…Several studies have reported that physical examination and imaging findings and related sensitivity and specifity findings about the detection of involved axillary lymph node(s) ( Table 3). Only imaging with mammography, US, and radionuclide techniques, including positron emission tomography, are currently inadequate or unnecessary; whether or not they are used alone or in combination [7,37,38]. Although providing more effective results, extensive axillary dissection and only sentinel lymph node dissection are cumbersome procedures requiring teamwork and leading to several drawbacks from hospitalization to a wide range of morbidities.…”