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α-二氟甲基鸟氨酸对雄激素依赖性前列腺肿瘤摄取¹⁴C-腐胺的增强作用。

alpha-Difluoromethylornithine enhancement of 14C-putrescine uptake by an androgen-dependent prostatic tumor.

作者信息

Heston W D, Kadmon D

出版信息

J Urol. 1986 Oct;136(4):944-8. doi: 10.1016/s0022-5347(17)45137-8.

Abstract

Putrescine is a potential scanning agent for metastases of prostatic carcinoma. We examined the in vivo uptake of [14C]-putrescine by the Dunning R3327H Copenhagen rat prostatic tumor and by other tissues, and conclude that: The uptake of [14C]-putrescine by the tumor was higher than that of the normal dorsolateral prostate, but similar to that of the ventral prostate. Tumor accumulation of [14C]-putrescine was enhanced 38% in intact and 45% in castrated animals by pretreatment with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor. Further enhancement of tumor uptake (94% in intact and 201% in castrated animals) was achieved by combining DFMO pretreatment with androgen stimulation. Oral administration of methyl-glyoxal bis (guanylhydrazone) (MGBG) increased intestinal uptake of [14C]-putrescine, while oral administration of unlabeled spermine and putrescine decreased it. Dexamethasone decreased the uptake of [14C]-putrescine by the spleen and intestine, but also reduced the prostatic uptake to a considerable extent. These observations are useful for the design of a putrescine-based scan for metastases of prostatic carcinoma.

摘要

腐胺是一种用于前列腺癌转移灶的潜在扫描剂。我们检测了[14C] - 腐胺在邓宁R3327H哥本哈根大鼠前列腺肿瘤及其他组织中的体内摄取情况,并得出以下结论:肿瘤对[14C] - 腐胺的摄取高于正常背外侧前列腺,但与腹侧前列腺相似。用多胺合成抑制剂α - 二氟甲基鸟氨酸(DFMO)预处理后,完整动物体内[14C] - 腐胺的肿瘤蓄积增加38%,去势动物增加45%。将DFMO预处理与雄激素刺激相结合,可进一步提高肿瘤摄取(完整动物提高94%,去势动物提高201%)。口服甲基乙二醛双(脒腙)(MGBG)可增加肠道对[14C] - 腐胺的摄取,而口服未标记的精胺和腐胺则会降低其摄取。地塞米松可降低脾脏和肠道对[14C] - 腐胺的摄取,但也会在很大程度上降低前列腺的摄取。这些观察结果有助于设计基于腐胺的前列腺癌转移灶扫描方法。

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