Radio-iodine-labelled 5-iodo-2-thiouracil: a potential radiopharmaceutical for establishing the viability of ocular melanoma after radiation therapy.

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.

Potential radiopharmaceuticals for the detection of ocular melanoma. Part II. Iodoquinoline derivatives and 67Ga-citrate.

The uptake and distribution of several 4-(substituted amino)-iodoquinolines, 131I-labelled, and of 67Ga-citrate were investigated in Syrian golden hamsters with Greene melanomas. Because of its uptake in the melanoma (tumour/eye ratio 8.9), 4-(dimethylamino-ethylamino)-7-iodoquinoline (NM113) was selected for further investigations as a possible radiopharmaceutical for ocular scintigraphy when labelled with 123I. High uptake of NM113 turned out to be incidental and could not be favourably influenced by several pharmacological pretreatments. Affinity for melanin, as shown in in vitro experiments, unfavourably influences NM113 tumour-to-eye ratios. In comparison with 67Ga-citrate, the latter, with a high tumour-to-eye ratio (44.8 after 24 h) is more promising in patient studies in which NM113 123I was not.

Uptake of 123I-5-iodo-2-thiouracil, a possible radiopharmaceutical for noninvasive detection of ocular melanoma, in melanotic and amelanotic melanomas in hamsters.

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.

Incorporation of [125I]-5-iodo-2-thiouracil in cultured hamster, rabbit, and human melanoma cells.

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.

Potential radiopharmaceuticals for the detection of ocular melanoma. Part I. 5-iodo-2-thiouracil derivatives.

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.