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An oestradiol-linked nitrosourea and site-directed chemotherapy in mammary carcinoma

Betsch, B.; Berger, M.R.; Spiegelhalder, B.; Schmähl, D.; Eisenbrand, G.

European Journal of Cancer 26(8): 895-898

1990

ISSN/ISBN: 0959-8049
PMID: 2145934
Document Number: 351055
The half-life, peak concentration, peak accumulation and tissue availability of the DNA-crosslinking nitrosourea 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) and its oestradiol-linked derivate (CNC-alanine-oestradiol-17-ester) were studied in liver, lung, spleen, uterus and mammary carcinomas in female Sprague-Dawley rats with chemically induced mammary carcinomas. Compared with CNC-alanine, the ester had a longer half-life, higher peak concentration, increased peak accumulation and enhanced tissue availability in all tissues. In oestradiol receptor positive mammary carcinomas, the oestradiol-linked drug showed a 2 times higher peak concentration, a 5 times longer half-life, a 10 times increased peak accumulation and a 20 times greater tissue availability compared with CNC-alanine. Oestradiol-linked nitrosoureas may offer new perspectives for site-directed chemotherapy of oestradiol receptor positive breast cancer.

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