Cytofluorescence localization of adriamycin in the nervous system. I. Distribution of the drug in the central nervous system of normal adult mice after intravenous injection

Abstract

By a fluorescence-microscopic technique the distribution of the antineoplastic glycoside, adriamycin (doxorubicin), was studied in the CNS of normal adult mice after i.v. injection. Doses comparable to those used in patients for the treatment of malignant diseases were used. The drug did not have access to areas of the brain within the blood-brain barrier but, except for the subcommissural organ, it was consistently localized in the nuclei of neurons and/or glial cells of the circumventricular organs (postremal area, subfornical organ, median eminence, neurohypophysis) as well as in cells of the choroid plexus and lamina cribrosa of the optic nerve. The nuclear fluorescence was accompanied by a less intense extracellular fluorescence when the survival time was shorter than 1 min after the injection. The fluorescence emitted by adriamycin was seen as early as 15 s after injection and showed its highest intensity at 1 and 15 min later. After 24 h fluorescence was no longer observed except for the ependymal zone of the median eminence. Our study thus shows that adriamycin passes from the blood into the nervous parenchyma in those areas of the brain located outside the blood-brain barrier. This finding raises the question whether in such regions there are any neurotoxicologic effects produced by the drug which have not yet been detected.