Coderre J A, Packer S, Fairchild R G, Greenberg D, Laster B, Micca P, Fand I
J Nucl Med. 1986 Jul;27(7):1157-64.
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.
硫脲嘧啶及其各种衍生物在生物合成过程中作为假黑色素前体被选择性地掺入黑色素瘤的黑色素中。利用BALB/c小鼠体内携带的可移植性哈丁-帕西黑色素瘤，我们扩展了之前用硫-35（³⁵S）硫脲嘧啶进行的研究。已证明[³⁵S]硫脲嘧啶在肿瘤中高水平持续长达2周；在此期间，正常组织中的药物含量恢复到接近背景水平。可用的多种碘同位素使碘硫脲嘧啶成为一种特别有前景的黑色素瘤定位剂。已比较了[³⁵S]硫脲嘧啶和碘硫脲嘧啶（碘-127（¹²⁷I）和碘-125（¹²⁵I）标记的）的肿瘤摄取和生物分布，发现基本相同。通过全身切片的放射自显影定性地证明了[¹²⁵I]硫脲嘧啶对黑色素瘤的选择性，并通过对肿瘤和选定组织的分析进行了定量。使用我们实验室目前正在开发的哈丁-帕西黑色素瘤的转移变体，还显示碘硫脲嘧啶定位于远处的继发性转移灶。这些研究证实了碘化硫脲嘧啶的黑色素瘤定位能力，因此也证实了使用碘化硫脲嘧啶衍生物诊断和治疗黑色素瘤的潜力。
