Uptake of adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas.
Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0.9 and 4.6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient. In an in vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.
von Holst
H
H
Department of Neurosurgery, Ludwig Institute for Cancer Research, Stockholm, Sweden.
Knochenhauer
E
E
Blomgren
H
H
Collins
V P
VP
Ehn
L
L
Lindquist
M
M
Norén
G
G
Peterson
C
C
D000328:Adult; D000368:Aged; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004317:Doxorubicin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004317:Doxorubicin