An oestradiol-linked nitrosourea and site-directed chemotherapy in mammary carcinoma.
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.
Betsch
B
B
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Berger
M R
MR
Spiegelhalder
B
B
Schmähl
D
D
Eisenbrand
G
G
D000409:Alanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D004958:Estradiol; C058788:N-(2-chloroethyl)-1-nitrosocarbamoylalanine; C056364:1-(2-chloroethyl)-1-nitrosocarbamoylalanine estradiol-17-ester; D000409:Alanine