RESUMEN
The aim of this study was the immunolocalization of transitional cell carcinoma of the bladder with a radiolabelled murine tumour-associated monoclonal antibody and the measurement of the absolute uptake of the antibody by the tumour. Fourteen patients with transitional cell carcinoma of the bladder received 3-6 mCi (111-222 MBq) of technetium-99m labelled HMFG1 monoclonal antibody intravesically and one patient, 2 mCi (74 MBq) of iodine-131 labelled 11.4.1, which is a non-tumour-specific monoclonal antibody. Four of the 15 patients were evaluated with single-photon emission tomography (SPET) 1 1/2 to 2 h post administration. All patients underwent transurethral resection of the bladder tumour within 12-20 h following intravesical administration of the radiolabelled antibody. The radioactivity of biopsy specimens from normal urothelium and tumour areas were counted in a gamma counter. The mean uptake of the radiolabelled antibodies from normal and tumour sites was expressed as a percentage of the administered dose per kilogram of tissue. Conventional histology and immunohistochemistry using HMFG1 monoclonal antibody were performed on paraffin sections of the biopsy specimens. Although our results are preliminary, it can be concluded that: (a) bladder tumours are well imaged by SPET when using 99mTc-HMFG1; (b) intravesically administered radiolabelled antibody remains on the bladder tissue and does not escape into the systemic circulation; (c) the wide range of tumour uptake values (0%-9.3% administered dose/kg) observed probably can be attributed to heterogeneity of the antigenic expression of the tumour; (d) values of 99mTc-HMFG1 monoclonal antibody uptake by the tumour do not justify future attempts at radioimmunotherapy.
Asunto(s)
Carcinoma de Células Transicionales/diagnóstico por imagen , Radioinmunodetección/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Administración Intravesical , Humanos , Radioisótopos de Yodo , Tecnecio , Factores de Tiempo , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The expression of a cell surface antigen recognized by the epithelium-specific, tumor-associated monoclonal antibody (Moab) AUA1 has been studied in 22 cases of normal urothelium, 7 cases of dysplastic urothelium and 86 cases of transitional cell carcinoma. Tissue specimens were stained with the conventional hematoxylin-eosin technique as well as with the indirect immunoperoxidase technique using Moab AUA1. Results showed that: (a) Moab AUA1 reacts mainly with cells of high or intermediate grade transitional cell carcinoma and with a restricted number of normal urothelial cells, and (b) antigenic heterogeneity exists between tumors of the same grade and within the same tumor.
Asunto(s)
Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Carcinoma de Células Transicionales/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Anticuerpos Monoclonales , Reacciones Antígeno-Anticuerpo , Epitelio/inmunología , Humanos , Inmunohistoquímica , Vejiga Urinaria/inmunologíaRESUMEN
Ten patients with transitional cell carcinoma (TCC) of the bladder received 3-6 mCi of HMFG1 monoclonal antibody (MAb) intravesically. The antibody was labeled with Tc-99m using the 2-Iminothiolane method. All patients underwent transurethral resection of the bladder tumor within 12-20 h following intravesical administration of 99m-Tc-HMFG1. The presence of the radiolabeled MAb in the circulation was studied by measuring the radioactivity in the serum for a period up to 20 h. Three of 10 patients underwent immunoscintigraphy (SPECT) 2-3 h postadministration and cancerous areas could be easily localized. Biopsies were taken from the tumor sites as well as from normal bladder mucosa. Absolute uptake of the administered MAb expressed as percent administered dose/kg of tissue could be evaluated only in eight patients. Multiple specimen taken from various tumor sites in every patient gave a wide range of uptake values ranging from 0 to 9.29% adm. dose/kg, whereas normal tissue uptake values ranged from 0 to 1.63, respectively.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Células Transicionales/terapia , Inmunoconjugados/uso terapéutico , Compuestos de Tecnecio/administración & dosificación , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Carcinoma de Células Transicionales/metabolismo , Epitelio/metabolismo , Humanos , Valores de Referencia , Compuestos de Tecnecio/farmacocinética , Distribución Tisular , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
The monoclonal antibody AUA1, labelled with 2 or 3 mCi iodine-131, was administered intravesically to 11 patients with known or suspected bladder carcinoma and was kept in the bladder for 1 h. All patients underwent immunoscintigraphy of the bladder at 2 h and three patients also at 20 h after instillation. Conventional histological and immunohistochemical examinations were performed on tissue samples from tumour and normal areas taken during cystoscopy, carried out 24-h after the instillation. Transitional cell carcinoma of the bladder was present in nine patients whereas dysplastic and normal urothelium was found in the remaining two patients, respectively. Six out of nine tumours were successfully imaged at the 2-h scan. Normal urothelium showed no uptake while dysplastic urothelium was positive on imaging. Successful detection was correlated with size and grade of tumour in almost all cases. Tumors with a diameter of 1 cm or less were not detected. Four out of five grade II tumours and two out of three grade III tumours were detected with this method. The method is a promising one although further studies using more suitable isotopes and/or monoclonal antibodies are required to increase its sensitivity.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma de Células Transicionales/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Animales , Carcinoma de Células Transicionales/patología , Humanos , Inmunoglobulina G/inmunología , Inmunohistoquímica , Radioisótopos de Yodo , Ratones , Proyectos Piloto , Cintigrafía , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Forty-five patients known or suspected to have transitional cell carcinoma of the urinary bladder underwent intravesical administration of either AUA1 tumor-associated monoclonal antibody or 11.4.1. nonspecific monoclonal antibody. Antibodies were radiolabeled with iodine-131, diluted in 50 ml normal saline and remained in the bladder for up to 1 h. During cystoscopy or transurethral resection of the tumor, tissue samples were taken from normal and malignant areas and were counted for radioactivity in a gamma counter. Blood samples were also measured for radioactivity. Mean uptake of AUA1 at 2, 20, 40 and 60 h after administration (expressed as 10(3) x percentage of injected dose/gram of tissue) was: 1.77 +/- 3.2, 1.28 +/- 1.67, 0.72 +/- 0.94 and 0, respectively in the tumor and 0.79 +/- 0.83, 0.14 +/- 0.34, 0.033 +/- 0.06 and 0 in normal tissue. Mean uptake of 11.4.1 at 2 and 20 h was: 0.47 +/- 0.42 and 0.018 +/- 0.015, respectively, in tumor and 0.2 +/- 0.19 and 0.013 +/- 0.002 in normal samples. No remarkable radioactivity was found in blood samples. Conventional and immunoperoxidase staining were also performed. Mean uptake of AUA1 by the tumor increased as the degree of tumor differentiation decreased. Our findings indicate that intravesical administration of AUA1 results in selective immunolocalization of AUA1 in intermediate and high-grade transitional cell carcinoma. This may allow the development of a new method for bladder carcinoma treatment or prophylaxis against recurrence.