Alpha-Difluoromethylornithine Enhancement of 14 C-Putrescine Uptake by an Androgen-Dependent Prostatic Tumor

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: 1) 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. 2) 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. 3) Further enhancement of tumor uptake (94% in intact and 201% in castrated animals) was achieved by combining DFMO pretreatment with androgen stimulation. 4) Oral administration of methylglyoxal bis (guanylhydrazone) (MGBG) increased intestinal uptake of [14C]-putrescine, while oral administration of unlabeled spermine and putrescine decreased it. 5) 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.