Melanin seeking compounds as melanoma localizing or therapeutic agents have a major limitation in that the normal melanin containing structures are frequently encountered clinically as background in the location of the tumor. This limits the usefulness of these compounds for therapy and diagnosis as they are bound to pre-formed melanin in both tumor and normal tissue. Our clinical experience with an iodine-123 labeled quinoline derivative was unsuccessful in localizing choroidal melanoma. This was in part due to the high background uptake of the melanin containing structures of the eye as well as the high uptake by the brain. However, the need in clinical ophthalmology for a melanoma localizing agent is now greater because of the increased use of radiotherapy wherein no tissue diagnosis is obtained. The difficulties in differentiating choroidal nevi from small malignant melanoma continues to plague opthalmology. Small animal data show that the false melanin precursor thioracil (TU) has a high concentration in Harding-Passey melanoma (about 10 percent dose/g), while retention in other tissues is about 100 times less. The uptake by other pigmented tissues such as the choroid of the eye is low, as incorporation of TU occurs only as melanin is being formed. The purpose of this study is to investigate the therapeutic and diagnostic potential of labeled thiouracil. Sulfur-35 labeled thiouracil has an absolute uptake in melanoma adequate for therapy. We wish to document therapeutic efficacy with animal studies. In addition, we will attempt to label thiouracil with iodine-123, selenium-75 and tellurium-123m for use in diagnosis. Biodistribution studies will be carried out as well as quantitative autoradiography. Therapeutic studies will be performed with the Harding-Passey melanoma in BALB/c mice and Greene melanoma in hamsters and rabbits. This group has clinical experience with both iodine-123 labeled quinoline and gallium-67 citrate that led to the development of a new detection system (dual eye probes). These probes maximized sensitivity and appeared to offer the best results. This system will be used with labeled thiouracil in the diagnosis of melanoma, and to evaluate the effects of therapy with S-35 labeled thiouracil. The objectives are to evaluate radiolabeled thiouracil for therapy and diagnosis in years 1 and 2, and to proceed to clinical diagnostic trials in year 3.
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