The clinical role of immunoscintigraphy for the detection of ocular melanoma.

The value of immunoscintigraphy in the diagnosis of choroidal melanoma is discussed and compared with other diagnostic procedures with isotopes and diagnostic modalities like fluorescein angiography, standardized ultrasonography and magnetic resonance imaging. Consecutive studies with immunoscintigraphy in choroidal melanoma show a sensitivity of 41 to 49%, which can be improved by use of single photon emission computerized tomography (SPECT). Another technique which has improved the results of radio-immunoscintigraphy is the use of a three-step labelling procedure with biotinylated anti-tumor antibodies and avidin. The specificity of the 225.28S antibody is discussed with regard to the expression of the chondroitin sulfate proteoglycan (CSPG)--to which the 225.28S antibody is directed--in normal tissue and in other malignant tumours.

Possibilities and limitations of radioimmunoscintigraphy and conventional diagnostic modalities in choroidal melanoma.

A prospective clinical study to assess the value of immunoscintigraphy with a monoclonal antibody (MoAb) against high molecular weight melanoma associated antigen (225.28S) was performed in 43 patients with choroidal melanoma; in six patients with a lesion suspected of being choroidal melanoma, and in seven patients with a benign lesion simulating a choroidal melanoma. The results of immunoscintigraphy in choroidal melanoma were compared with results of conventional diagnostic modalities like ultrasonography and fluorescein angiography. Planar scintigraphy showed a detection rate of 49% which is comparable with other studies. The detection with scintigraphy was correlated to the size of the choroidal melanoma. The use of single photon computed tomography did not increase the sensitivity of immunoscintigraphy. Ultrasonography yielded a correct diagnosis in 37 of 42 melanomas (88%). With fluorescein angiography a correct diagnosis was obtained in 11 of 30 melanomas (36.6%). The value of immunoscintigraphy with MoAb 225.28S in small choroidal melanomas is limited; its reliability increases in large tumours. Immunohistochemistry with MoAb 225.28S showed antigen expression in 95% of the stained tissue specimens of choroidal melanoma.

Dosimetry of ruthenium-106 eye applicators.

In view of the importance of clinical applications of ruthenium-106 beta-ray sources for the treatment of choroidal melanoma, experimental, and theoretical approaches are presented for the dosimetry of such sources. The absolute dose and percentage depth dose of ruthenium applicators have been measured with an extrapolation ionization chamber. For a special flat applicator the absolute dose could be measured with an accuracy of +/- 5%, which is determined by the collection efficiency of the extrapolation chamber. The percentage depth dose of concave applicators, employed in the clinical situation, could only be measured at a distance larger than 5 mm due to their geometry and the outer dimensions of the extrapolation chamber. A computer simulation was therefore developed for the absorption and scattering of electrons, taking into account the geometry and materials of the applicator, to predict the percentage depth dose at distances smaller than 5 mm. The calculated and experimentally determined depth doses are in good agreement. With the aid of the computer simulation a depth dose determination for concave applicators can be made for clinically relevant distances less than 10 mm from the source surface with an absolute accuracy of +/- 10%.

The clinical status of immunoscintigraphy with monoclonal antibodies in ocular melanoma.

A summary is given of data on the clinical experience with the anti-melanoma antibody 225.28S in ophthalmology and the tissue expression of the high molecular weight-melanoma associated antigen in choroidal melanoma. Results are discussed in relation to other detection methods for ocular melanoma currently employed by the ophthalmologist.

Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results.

Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy.

Intracerebral uptake of Tc-99m labeled antimelanoma antibodies.

A patient with an intraocular tumor showed accumulation of Tc-99m labeled antimelanoma antibodies in the head. This was not due to a metastatic lesion but proved to be a benign intracranial osteoma. The reasons for this false-positive result are discussed.

[Immunoscintigraphy of choroid melanoma using monoclonal antibodies]. / Immunoscintigrafie van het choroideamelanoom met behulp van monoklonale antilichamen.

A prospective pilot study on immunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was performed in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma associated antigen were labelled with 740 mBq (20 MCi) of the radionuclide 99mTc and injected intravenously. Images were made with a gamma camera 6 hours after injection. With a double pinhole collimator radioactivity was counted thrice in both eyes 6 hours after injection. In 6 out of 17 patients (35.3%) the melanoma could be imaged with the gamma camera. With the double pinhole collimator a significantly higher activity was measured in the melanomatous eye in 13 out of 17 patients (76.5%). In four patients a false negative result was obtained. Considering these results immunoscintigraphy may be valuable in ocular melanoma diagnostics but its specific value still has to be assessed.

Radioimmunoscintigraphy with melanoma-associated monoclonal antibody fragments in choroidal melanoma.

A prospective pilot study on radioimmunoscintigraphy with monoclonal antibody fragments against cutaneous melanoma (MoAb 225.28S) was carried out in 17 patients with a clinical diagnosis of choroidal melanoma. Monoclonal antibodies against melanoma-associated antigen were labeled with 740 mBq 99mTc and injected IV; images were made with a gamma camera at 6 h after injection. With a double-pinhole collimator, radioactivity was counted thrice in both eyes at 6 h after injection. In 6 of 16 patients (37.5%), the melanoma could be imaged with the gamma camera. With the double-pinhole collimator, a significantly higher activity was measured in the melanomatous eye in 13 of 16 patients (82.4%). In two patients a false negative result was obtained, and in one patient the difference between the left and right eye was not significant. Considering these results, radioimmunoscintigraphy may be valuable in ocular melanoma diagnostics, but the specificity of MoAb 225.28S needs to be assessed.

Effect of beta-irradiation by a 106 ruthenium plaque on the rabbit eye choroid.

Fourteen Chinchilla gray rabbit eyes were treated with a ruthenium plaque, receiving 200, 400, or 800 Gy, to assess the effect of beta-irradiation on the normal rabbit choroid. Radiation effects were evaluated using fundus photography, fluorescein angiography, fluorophotometry, and histology. Fluorophotometry showed a fluorescein leakage into the vitreous 1 day after irradiation. Leakage values returned to normal within 1 month after irradiation. Fluorescein angiography showed nonperfusion of the choroid after beta-irradiation; the time between irradiation and the onset of nonperfusion was found to be dose dependent. Five months after 200 Gy irradiation, choroidal atrophy had developed but some vessels still stained with fluorescein; 400 Gy irradiation induced subtotal choroidal nonperfusion within 3 months and 800 Gy within 1 week.