Uptake and Distribution of the Estramustine-Phosphate Metabolite Estramustine after Single-Dose Injection in Patients with Prostatic Cancer

Abstract

The concentration of estramustine (EaM) in serum and tumor tissue of 19 patients with prostatic carcinoma was determined after single i. v. injection of estramustine phosphate (300 or 600 mg) administered 12 to 15.5 hours prior to radical prostatectomy. The concentration (mean ± SD) was 21.9 ± 10.3 ng/ml in serum and 234 ± 168 ng/g in the tumor tissue. In patients treated with 300 mg the tumor tissue: serum ratio was decreased (12.0: 1 for 600 mg and 5.4: 1 for 300 mg, respectively). EMBP was detected in 18/19 (95 %) of the specimens, levels were positively correlated both with the tumor: serum ratio (r = 0.48) and the absolute tumor concentration (r = 0.62). Specific binding of EaM was obtained in 18/19 (95 %) of the specimens. The study is the first to show that the cytotoxically active metabolite estramustine is concentrated in prostatic tissue after single dose i.v. injection and that there might be a dose-dependent effect on the concentration. The concept of an estramustine binding protein that causes the selective binding and uptake of EaM in prostatic tissue is further supported by our results.