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

Abstract

Summary HMFGI tumour associated monoclonal antibody IgGl and F(ab')2 fragments were radiolabelled with indium-111 and used to study patients with breast cancer. In vitro and in vivo stability of the radiolabelled antibodies was shown to be satisfactory. Thirty patients with primary breast cancer underwent tumour resection and quantitative evaluation of the radioactivity in the tumour and normal tissues following administration of specific and non-specific antibodies. The mean tumour uptake of HMFG1 F(ab')2 fragments at 24h was significantly higher (P<0.05) than the intact IgG but at 48h there was no difference. The mean tumour uptake with the specific antibody was higher than the non-specific antibody of the same subclass (P<0.05). Lymph node metastases showed higher antibody uptake than the corresponding primary tumours (P<0.05). Fifteen patients with primary or metastatic breast cancer were investigated by external body scintigraphy using HMFG1 F(ab')2 fragments. Successful localisation was observed in approximately 50% of the primary and metastatic lesions with no false positive results. All the patients had observable concentration of "'1In in the liver (20% of the injected dose), the kidneys and the spleen. Following i.v. administration, F(ab')2 fragments cleared from the blood more rapidly than the intact IgG. We conclude that HMFG1 F(ab')2 fragments can localise specifically and faster than intact IgG in breast cancer but the sensitivity of the radioimmunoscintigraphy is relatively low. This method needs further improvement before becoming clinically useful for detecting and staging breast cancer.

Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124iodine in patients with breast cancer

“…However, in order to accurately calculate dosimetry, absolute quantification is necessary. This has been possible previously only by measuring uptake in biopsied material following tracer administration (Epenetos et al, 1986;Kalofonos et al, 1989). Positron emission tomography (PET), because of its improved sensitivity and correction for tissue attenuation, allows for accurate quantitation (Beaney, 1984).…”

“…We report on the use of PET and Iz4I for the quantitative and temporal measurement of MAb uptake in breast tumours and in normal tissues. HMFGl was chosen as the initial antibody under investigation, since biodistribution in surgical specimens has already been evaluated in our unit (Kalofonos et al, 1989), and because of its already extensive use in clinical imaging and therapy (Epenetos et al, 1982(Epenetos et al, , 1987Stewart et al, 1989). Tumour blood flow was also measured in all cases in order to assess its importance on antibody delivery.…”

Characterization of Monoclonal Antibodies Reactive with Normal Resting, Lactating and Neoplastic Human Breast

“…They have been implicated as markers of prognosis [9,10] and histologic and cytologic diagnosis of cancer [11]. They have been used to detect raised levels of breast antigens in the sera of breast cancer patients [12][13][14][15][16][17][18][19], to radiolocalize breast carcinomas [20][21][22][23] and to semiquantify estrogen receptors in breast carci nomas [24]. They have also been evaluated for their role in the development of breast cancer immunotoxins [3], A common observation has been that morphologically identical cells show hetero geneity in antigen expression.…”

Monoclonal Antibody Targeting of Ovarian Carcinoma

“…However, the results may not be even ideal if antibody transport to the tumour site is impaired as a result of adhesions or disturbance of vascular supply and lymphatic drainage from previous extensive intra-abdominal surgery, as it is usually the case in ovarian cancer. Antibody fragments [F(ab)) 2 , Fab) or single chain Fv domains] may show better accessibility profiles and provide improved tumour to normal tissue ratios, thus allowing better RIL results [35][36][37][38]. Recently, conjugation of monomeric Fab) fragments to polyethylene glycol has been shown to result in a dramatic enhancement of the area under the concentration-time curve in the tumour compared to normal tissue, thus raising very promising expectations regarding radioimmunotherapy [39].…”