A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

Dencker, Lennart; Larsson, Bengt; Olander, Karin; Ullberg, Sven

doi:10.1038/bjc.1982.12

Cited by 34 publications

(13 citation statements)

References 6 publications

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“…Administration of 1251-TU gave higher radioactivity concentrations in the thyroid than would have been expected if 125I-TU would accumulate in the thyroid to the same extent as we had earlier observed for 14C-labelled thiouracil (Dencker et al, 1982). This could be due to partial deiodination of 125I-TU.…”

Section: As Can Be Seen In the Figure And Insupporting

confidence: 67%

“…The thyroid uptake (in % g dose per g tissue) of radioactivity after 1251-TU injection (Table II) was then reduced by our earlier value after 14C-thiouracil injection (Dencker et al, 1982). This gives the approximate contribution of free 1251 to the thyroid radioactivity concentration after 1251-TU administration.…”

Section: Experimental Groupsmentioning

confidence: 64%

“…in the eyes of foetuses or young animals and in melaninproducing tumours (Whittaker, 1971;Dencker et al, 1979Dencker et al, , 1981Dencker et al, , 1982. Unlike drugs such as chloroquine and chlorpromazine (Lindquist & Ullberg, 1972), thiouracil does not bind to preformed melanin.…”

Section: In Earlier Studies It Was Shown Thatmentioning

confidence: 99%

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Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas

Larsson¹,

Olander²,

Dencker³

et al. 1982

Br J Cancer

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We have shown that thioamides are incorporated as false precursors into melanin during its synthesis. To be clinically useful in the diagnosis or therapy of melanotic melanomas, they would have to be tagged with an appropriate isotope or possibly a cytotoxic moiety. 125I-Thiouracil (125I-TU) is here shown to be accumulated in the melanin of melanotic melanomas transplanted into mice in a similar way as is 14C-thiouracil (14C-TU). 125I-TU gives tumour/liver and tumour/muscle ratios up to 22 and 778 respectively, at 4 days after administration. 125I-TU is accumulated by melanoma cells in vitro more effectively than 14C-TU (125I-TU/14C-TU, 2.7), while the in vivo accumulation into melanomas is slightly lower for 125I-TU as compared to 14C-TU (125I-TU/14C-TU, 0.35). This appears to be due to a partial deiodination (less than 14% of the dose within 4 days) and probably a more rapid excretion of 125I-TU or its metabolite(s). The accumulation of radioactivity in the thyroid can essentially be eliminated by pretreatment with potassium iodide and/or thyroxine. 125I-Propylthiouracil is also accumulated in melanotic melanoma cells in vivo and in vitro, but at a lower level than in 125I-TU and 14C-TU. Images Fig.

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Section: As Can Be Seen In the Figure And Insupporting

confidence: 67%

Section: Experimental Groupsmentioning

confidence: 64%

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Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas

Larsson¹,

Olander²,

Dencker³

et al. 1982

Br J Cancer

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“…In view of reports that inhibition of melanin synthesis suppressed the growth of rodent melanomas (Demopoulous, 1973;Pawelek, 1976;Prabhakaram et ai, 1969), it was of interest that PTU strongly inhibited tyrosinase activity in MM418 cells without being excessively toxic. The lack of additional toxicity by the ^"^C compounds, in particular by ^'C-TU in MM418 cells, is not considered a significant problem at the present stage of investigation because of the possibility of using higher specific activities of ^"^C-TU or of using '25i-labelled material (Broxterman et al, 1983;Dencker et al, 1982;Larsson et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies in rodents have documented the selective uptake of CPZ and related compounds by cells containing melanin (Blois, 1965;Fairchild et al, 1982a;Nakanishi, Ichihashi and Mishima, 1981;Nakanishi etal, 1980;Potts, 1964) and of TU by cells actively synthesizing melanin (Broxterman et al, 1983;Dencker et al, 1979;Dencker et al, 1982;Fairchild et al, 1982b;. Encouraging results have been obtained supporting a possible diagnostic and/or therapeutic role of radiopharmaceutical analogues for malignant melanoma.…”

Section: Introductionmentioning

confidence: 98%

Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

Parsons

Allen

1986

Aust J Exp Biol Med

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Summary.The uptake (total radioactivity in intact cells) and incorporation (radioactivity bound to acid-precipitable material) of '^C-chlorpromazine (CPZ) and '•'C-thiouracil (TU) were studied using a library of 3 human fibroblast strains and 13 tumour cell lines. In contrast to previous studies using rodent melanomas in vivo, the melanoma lines, including lines with high tyrosinase and melanin contents, did not take up more CPZ and TU than non-melanoma cells (fibroblasts, HeLa cells). Incorporation of CPZ was also broadly similar in all cell types studied. TU was selectively incorporated into the melanoma line having a high tyrosinase and melanin content but not into lines with high tyrosinase activity and low melanin content. While supporting the possibility of selective therapy for heavily-pigmented melanomas using labelled TU derivatives, these results suggest that the action of potentially melanoma-affined compounds should be further evaluated in human cells. Unlabelled CPZ or TU was not selectively toxic to melanoma cells. Unexpectedly, methylation-sensitive tumour cells (Mer" phenotype) were highly resistant to TU, thus providing a new experimental tool for understanding the genesis of this phenotype in vivo.

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Detection of Melanomas

Levine¹

1983

Arch Dermatol

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A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

Cited by 34 publications

References 6 publications

Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas

Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas

Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

Detection of Melanomas

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