thiouracil and iodothiouracil

Positron emission tomography (PET) has evolved as a new diagnostic modality in cancer patients. Thioureylenes, such as thiouracil and methimazole, are known to be incorporated into growing melanin and selectively retained in melanotic melanoma. In the present study we used [(76)Br]5-bromo-2-thiouracil as tracer for PET imaging of human and murine melanotic melanoma transplanted subcutaneously into rats. The melanomas were clearly depicted 1 day after the injection, when [(76)Br]5-bromo-2-thiouracil was retained in the tumors though the overall radioactivity concentration in the body had declined. Accumulation of (76)Br was also seen in bladder, liver, and kidney. In addition, the rats were simultaneously injected with [(125)I]5-iodo-2-thiouracil and the tissue distribution of radioactivity was mapped by whole-body autoradiography. The results confirmed the selective uptake of thiouracil in the melanoma where the concentration of (125)I-radioactivity was about three-fold higher than that in the liver and lungs. These results show the possibility of using [(76)Br]5-bromo-2-thiouracil for PET diagnostics of melanoma, including dosimetry, prior to targeted therapy using [(131)I]5-iodo-2-thiouracil or [(211)At]5-astato-2-thiouracil.

Topics: Animals; Autoradiography; Bromine Radioisotopes; Humans; Iodine Radioisotopes; Male; Melanoma, Experimental; Mice; Neoplasm Transplantation; Radiopharmaceuticals; Rats; Rats, Nude; Thiouracil; Tissue Distribution; Tomography, Emission-Computed; Transplantation, Heterologous

5-Iodo-2-thiouracil (ITU) is of interest due to its ability to bind specifically to the pigment melanin during melanogenesis and is of potential value in the diagnosis and treatment of malignant melanoma. Radioiodinated ITU was prepared directly from 2-thiouracil in a two-phase reaction using Iodo-Gen in 0.05 M phosphate buffer pH 7.0. The identity radiochemical purity and stability of the product were checked by reversed-phase high pressure liquid chromatography (HPLC). ITU labeled with 123I, 125I or 131I has been produced in millicurie amounts and isolated on a semi-preparative reversed-phase HPLC column. Production time was 2-3 h, overall radiochemical yields averaged 80%; the radiochemical purity was greater than 98%. Specific activities on the order of 20 Ci/mmol have been obtained.

Topics: Animals; Chromatography, High Pressure Liquid; Humans; Iodine Radioisotopes; Melanins; Melanoma; Radiochemistry; Radionuclide Imaging; Thiouracil; Urea

Topics: Humans; Iodine Radioisotopes; Melanoma; Radionuclide Imaging; Thiouracil

Radio-iodine-labelled thiouracil has been evaluated as a radiopharmaceutical for establishing the viability of ocular melanoma after radiation treatment. The uptake of 125I-5-iodo-2-thiouracil (125I-ITU) was studied in X-ray irradiated and non-irradiated melanotic melanomas implanted in Syrian golden hamsters. Uptake of 125I-ITU in melanomas 4 days after irradiation with 40 Gy X-ray was 25% of the value found in non-irradiated controls, 12 days after such treatment it was 10% of that value. Twenty-one days after radiation treatment the melanomas showed regrowth and uptake of 125I-ITU was about equal to that in non-treated controls. Uptake of 125I-ITU in melanomas after 10 Gy X-ray irradiation was higher and uptake in tumours after 20 Gy was only slightly lower than the uptake by non-irradiated melanomas. The results indicate that the iodine labelled-thiouracil uptake test may be useful as an additional diagnostic issue for assessing the viability of ocular melanoma after radiation therapy.

Topics: Animals; Choroid Neoplasms; Cricetinae; Iodine Radioisotopes; Melanoma; Mesocricetus; Radionuclide Imaging; Thiouracil

[123I]-5-iodo-2-thiouracil (123I-ITU) was evaluated as a radiopharmaceutical for tumor detection in 10 patients with proven choroidal melanoma. Uptake of 123I-ITU was measured with a specially designed single eye probe collimator, 24 h after administration of 123I-ITU. Increased uptake in the tumor-bearing eye as compared to the fellow nontumor bearing eye was found in 7 out of 10 cases when the probe was located 3.5 cm in front of the eye (p less than 0.01). By using a double pinhole collimator tests were positive in 3 out of 10 123I-ITU studies only. Tests with 123I-ITU were compared with 67Ga tests in the same patients. The 67Ga tests with the single eye probe collimator were positive in 6 out 10 cases when the probe was located 6 cm in front of the eye. With the double pinhole collimator tests were positive in 7 out of 10 67Ga studies. It is concluded that 123I-labeled thiouracil is at least as useful as a radiopharmaceutical for ocular melanoma diagnosis as 67Ga-citrate, provided measurements are performed with a single eye probe.

Topics: Choroid Neoplasms; False Positive Reactions; Gallium Radioisotopes; Humans; Melanoma; Radionuclide Imaging; Thiouracil

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.

Topics: Animals; Female; Iodine Radioisotopes; Melanoma; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Radionuclide Imaging; Sulfur Radioisotopes; Thiouracil; Tissue Distribution

The uptake of 123I-5-iodo-2-thiouracil in melanotic and amelanotic melanoma implanted in Syrian golden hamsters was studied. A selective accumulation was found in the tumours. Uptake of 123ITU in melanotic melanomas was 4 to 5 times the uptake in amelanotic ones. For both tumours high ratios of tumours versus non-tumour were found. The high accumulation of 123ITU in both kinds of tumours and the high tumour versus non-tumour ratios suggest that 123ITU may be a promising radiopharmaceutical for the detection of ocular melanoma.

Topics: Animals; Cricetinae; Eye Neoplasms; Iodine Radioisotopes; Male; Melanoma; Mesocricetus; Radionuclide Imaging; Thiouracil

The incorporation of [2-14C]-2-thiouracil and a series of [125I]-5-iodo-2-thiouracils ([125I]ISUra(s)) into cultured Greene hamster melanoma cells was determined in order to establish their properties as false precursors in the melanin-biosynthetic pathway. The cold trichloroacetic acid-precipitable incorporation of [2-14C]-2-thiouracil as well as [125I]ISUra into melanoma cells after a 24- to 48-hr labeling period proved to be completely tyrosinase dependent (more than 99.5% inhibition could be achieved by 0.5 mM phenylthiourea). [125I]ISUra incorporation was 3-fold higher than was [2-14C]-2-thiouracil incorporation and was enhanced by 1 mM theophylline treatment. [125I]ISUra incorporation into hamster, rabbit, and human melanoma cells showed a linear relationship with cell melanin content. Methylation of the sulfur completely prevented the incorporation, while propylation but not methylation at position 6 resulted in lower incorporation. [125I]ISUra proved to be a marker for melanogenesis and may be useful in studies on the differentiation of cultured melanoma cells.

Topics: Animals; Cell Division; Cells, Cultured; Cricetinae; Humans; Melanins; Melanoma; Phenylthiourea; Rabbits; Thiouracil

The tissue distribution of a number of 5-[131I]-iodo-2-thiouracil derivatives was measured in Syrian golden hamsters with Greene melanoma. These compounds were rapidly (in less than 1 h) distributed in all tissues, while in most tissues fast elimination (T1/2 1-3 h) was observed. Because of retention of the 131I activity in the tumour, high tumour/non-tumour tissue ratios were found (e.g. tumour/eye 2.3-10, tumour/skin 1.5-3) suggesting that some of these compounds might be used as melanoma delineating agents, when labelled with 123I.

Topics: Animals; Cricetinae; Eye Neoplasms; Iodine Radioisotopes; Male; Melanoma; Mesocricetus; Neoplasm Transplantation; Neoplasms, Experimental; Radionuclide Imaging; Thiouracil; Tissue Distribution

Topics: Thiouracil

Topics: Hyperthyroidism; Perchlorates; Potassium; Potassium Compounds; Thiouracil; Thyrotoxicosis

Topics: Goiter; Hyperthyroidism; Thiouracil; Thyrotoxicosis

Topics: Thiouracil; Thyroid Gland; Viscera

Topics: Blood; Thiouracil

Topics: Humans; Hyperthyroidism; Thiouracil

Topics: Hyperthyroidism; Potassium Iodide; Sodium; Thiouracil

Topics: Body Fluids; Halogenation; Humans; Iodides; Iodine; Thiouracil

Topics: Barbiturates; Humans; Phenobarbital; Pruritus; Thiouracil

Topics: Antithyroid Agents; Epithelium; Thiouracil; Thyroid Gland; Viscera

Topics: Antithyroid Agents; Biological Products; Humans; Iodides; Iodine; Iodine Radioisotopes; Thiouracil; Thyroid Gland

Topics: Diagnostic Tests, Routine; Health Services; Humans; Iodides; Iodine; Thiouracil

Topics: Animals; Oxygen; Oxygen Consumption; Rats; Thiouracil

Topics: Thiouracil; Thyroid Gland

Topics: Hyperthyroidism; Sodium; Sodium, Dietary; Thiouracil

Topics: Antithyroid Agents; Humans; Thioglycolates; Thiouracil; Thiourea; Thyroid Gland