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Immunoscintigraphy in primary intraocular malignant melanoma
Abstracts
182
Immunoscintigraphy in FVimary Intraocular Malignant Melanoma* K. SCHEIDHAUER, G. LEINSINGER, E. MOSER, 0. F. SCHEIFFARTH, K. RIEDEL and F. H. STEFANI
Departments of Radiology (Klinikum Grosshadem) and Ophthalmology, University of Munich, F.R.G. Early diagnosis of malignant tumors is mandatory for their successful therapy. Eye melanoma is the most common primary ocular tumor. Diagnosis of these small-sized lesions is usually made by ophthalmoscopy and ultrasound in early stages due to visual symptoms. Therefore, the main attempt of this study was to evaluate immunoscintigraphy (IS) of eye melanoma for visualizing small lesions. A further goal was to show the superiority of single photon emission CT (SPECT) in comparison to the conventional planar scintigraphy in IS. Thirty nine patients with eye tumors were studied using *Tc labeled F(ab’), fragments of the antimelanoma monoclonal antibody 225.283 (Tecnemab-1, Sorin Biomedica), which recognize the highmolecular-weight melanoma-associated antigen. Size of lesions ranged from 2.0 to 10.8 mm (mean: 6.2 mm), measured by ophthalmoscopy and ultrasound. In 37 cases, eye melanoma was confirmed; in 2 patients, benign nevi were diagnosed. IS was performed up to 24 h after i.v. injection of 0.3 mg of the IgG,, monoclonal antibody labelled with 400-600 MBq %Tc. No side effects were observed. Specificity of the anti-melanoma antibody was studied in two patients by simultaneous injection of an “‘In labelled CEA-specific antibody (IgG,, fragments like 225.288) and simultaneous measurement. Scintigrams were taken in planar mode (ventral view) as well as by SPECT. Acquisition time was up to 40 min with both modalities, in which at least 150,000 total counts were collected. The recognized antigen was proven by immunohistochemical methods (immunofluorescence) in nine enucleated melanomas. 15/37 (41%) of the documented intraocular melanomas were visualized by planar scintigraphy. Using SPECT, 27/37 (73%) lesions were detected. Detectability was independent from nasal or temporal localization. The benign lesions showed no antibody uptake. These data confirm the potential of IS to detect even small lesions (< 11 mm); SPECT is superior compared to planar scans (73 vs 41% true positive results). Although the data on specificity are not yet sufficient, IS may become helpful in differential diagnosis of intraocular tumors.
Radiolabelled Moooclonal Antibodies for Therapy of Ovarian Cancer A. A. EPENETOS Senior Lecturer and Consultant in Clinical Oncology, Royal Postgraduate Medical School, London
Administration of a lethal dose of radiation to tumour cells while sparing normal tissue is the ideal aim in radiotherapy. The closest we come to this ideal is in the treatment of thyroid carcinoma where tumour cells take up and concentrate iodine 131. Although thyroid carcinoma is not particularly radiosensitive, the dose is so great that the tumour cells are destroyed with minimal toxicity to normal tissue. Unfortunately, no other tumour behaves quite like this and we must rely on external beam irradiation where the tolerated dose is much less. On the surface of all cells are complex molecules called antigens by which different cell types can be distinguished. Although no one has yet discovered an antigen specific for tumour cells, some malignant cells possess greater amounts of a particular antigen. These are called “tumour associated antigens” and are the target for monoclonal antibodies. Monoclonal antibodies are antibodies that react against only one antigen. They are manufactured by an immortal clone of cells derived from mice that have been immunised with the antigen concerned. These antibody-producing cells are immortalised by fusing them with myeloma cells to produce a hybridoma. Each hybridoma will produce a different clone of cells each with its own monoclonal antibody. One of these clones is selected to grow in culture, and the monoclonal antibody harvested. Initially, it was thought that monoclonal antibodies may destroy tumour cells by adhering to the surface and activating the immune system. This occured in one lymphoma patient who achieved complete response lasting more than 4 years. However, no other patients have responded as well and this must be considered a rare event. Monoclonal antibodies have also been given to patients with carcinoma of the colon and melanoma but the partial responses obtained were uncommon and short lived. As it is clear that monoclonal antibodies cannot easily destroy tumours by using the immune system, several workers have attached radioactive isotopes, anti-cancer drugs or toxins to the other end of the antibody in the hope that these will kill the cell the antibody adheres to. Radioisotopes such as iodine-131, yttrium-90 and phosphorous-32
can all he attached
to monoclonal
antibodies
so that the antibody
will irradiate
*These studies were carried out as a clinical trial and supported by a grant from the Deutsche Krebshilfe.
the
182
Immunoscintigraphy in FVimary Intraocular Malignant Melanoma* K. SCHEIDHAUER, G. LEINSINGER, E. MOSER, 0. F. SCHEIFFARTH, K. RIEDEL and F. H. STEFANI
Departments of Radiology (Klinikum Grosshadem) and Ophthalmology, University of Munich, F.R.G. Early diagnosis of malignant tumors is mandatory for their successful therapy. Eye melanoma is the most common primary ocular tumor. Diagnosis of these small-sized lesions is usually made by ophthalmoscopy and ultrasound in early stages due to visual symptoms. Therefore, the main attempt of this study was to evaluate immunoscintigraphy (IS) of eye melanoma for visualizing small lesions. A further goal was to show the superiority of single photon emission CT (SPECT) in comparison to the conventional planar scintigraphy in IS. Thirty nine patients with eye tumors were studied using *Tc labeled F(ab’), fragments of the antimelanoma monoclonal antibody 225.283 (Tecnemab-1, Sorin Biomedica), which recognize the highmolecular-weight melanoma-associated antigen. Size of lesions ranged from 2.0 to 10.8 mm (mean: 6.2 mm), measured by ophthalmoscopy and ultrasound. In 37 cases, eye melanoma was confirmed; in 2 patients, benign nevi were diagnosed. IS was performed up to 24 h after i.v. injection of 0.3 mg of the IgG,, monoclonal antibody labelled with 400-600 MBq %Tc. No side effects were observed. Specificity of the anti-melanoma antibody was studied in two patients by simultaneous injection of an “‘In labelled CEA-specific antibody (IgG,, fragments like 225.288) and simultaneous measurement. Scintigrams were taken in planar mode (ventral view) as well as by SPECT. Acquisition time was up to 40 min with both modalities, in which at least 150,000 total counts were collected. The recognized antigen was proven by immunohistochemical methods (immunofluorescence) in nine enucleated melanomas. 15/37 (41%) of the documented intraocular melanomas were visualized by planar scintigraphy. Using SPECT, 27/37 (73%) lesions were detected. Detectability was independent from nasal or temporal localization. The benign lesions showed no antibody uptake. These data confirm the potential of IS to detect even small lesions (< 11 mm); SPECT is superior compared to planar scans (73 vs 41% true positive results). Although the data on specificity are not yet sufficient, IS may become helpful in differential diagnosis of intraocular tumors.
Radiolabelled Moooclonal Antibodies for Therapy of Ovarian Cancer A. A. EPENETOS Senior Lecturer and Consultant in Clinical Oncology, Royal Postgraduate Medical School, London
Administration of a lethal dose of radiation to tumour cells while sparing normal tissue is the ideal aim in radiotherapy. The closest we come to this ideal is in the treatment of thyroid carcinoma where tumour cells take up and concentrate iodine 131. Although thyroid carcinoma is not particularly radiosensitive, the dose is so great that the tumour cells are destroyed with minimal toxicity to normal tissue. Unfortunately, no other tumour behaves quite like this and we must rely on external beam irradiation where the tolerated dose is much less. On the surface of all cells are complex molecules called antigens by which different cell types can be distinguished. Although no one has yet discovered an antigen specific for tumour cells, some malignant cells possess greater amounts of a particular antigen. These are called “tumour associated antigens” and are the target for monoclonal antibodies. Monoclonal antibodies are antibodies that react against only one antigen. They are manufactured by an immortal clone of cells derived from mice that have been immunised with the antigen concerned. These antibody-producing cells are immortalised by fusing them with myeloma cells to produce a hybridoma. Each hybridoma will produce a different clone of cells each with its own monoclonal antibody. One of these clones is selected to grow in culture, and the monoclonal antibody harvested. Initially, it was thought that monoclonal antibodies may destroy tumour cells by adhering to the surface and activating the immune system. This occured in one lymphoma patient who achieved complete response lasting more than 4 years. However, no other patients have responded as well and this must be considered a rare event. Monoclonal antibodies have also been given to patients with carcinoma of the colon and melanoma but the partial responses obtained were uncommon and short lived. As it is clear that monoclonal antibodies cannot easily destroy tumours by using the immune system, several workers have attached radioactive isotopes, anti-cancer drugs or toxins to the other end of the antibody in the hope that these will kill the cell the antibody adheres to. Radioisotopes such as iodine-131, yttrium-90 and phosphorous-32
can all he attached
to monoclonal
antibodies
so that the antibody
will irradiate
*These studies were carried out as a clinical trial and supported by a grant from the Deutsche Krebshilfe.
the