Intratumoral differences in methotrexate levels within human osteosarcoma xenografts studied by microdialysis

A central tenet in oncology is the assumed relationship between drug concentration and cytotoxicity. Determinations of drug levels in tumor tissues are, however, generally not undertaken. Microdialysis is a method where continuous drug monitoring may be achieved by sampling of low molecular weight s...

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Bibliographic Details
Published in:Life sciences (1973) 1997, Vol.61 (19), p.PL275-PL280
Main Authors: Ekstrøm, Per O., Giercksky, Karl E., Andersen, Anders, Bruland, Øyvind S., Slørdal, Lars
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - pharmacokinetics
Area Under Curve
Bone Neoplasms - metabolism
Humans
Male
methotrexate
Methotrexate - pharmacokinetics
Microdialysis
Neoplasm Transplantation
nude rat
osteosarcoma
Osteosarcoma - metabolism
Rats
Rats, Nude
tissue
Transplantation, Heterologous
Tumor Cells, Cultured
xenograft
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Summary:A central tenet in oncology is the assumed relationship between drug concentration and cytotoxicity. Determinations of drug levels in tumor tissues are, however, generally not undertaken. Microdialysis is a method where continuous drug monitoring may be achieved by sampling of low molecular weight substances from the extracellular space. By employing this technique it is possible to observe variable drug levels within tissues, including tumors, over time. Herein, we present results from a nude rat model where subcutaneous human osteosarcoma xenografts were established prior to the administration of the antifolate methotrexate as an intravenous infusion. Significant differences in drug exposure within single tumors were evident. Generally, peak drug concentrations were lower and drug efflux slower from the center of the tumors as compared to the periphery. The use of microdialysis could be an important tool for optimizing current strategies in anticancer chemotherapy.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(97)00839-4