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Cerebral microdialysis is used to study anticancer drug penetration in the central nervous system (CNS) and brain tumors in animal models. Genetically engineered murine models (GEMMs) have been recently used to study many aspects of CNS tumors since they represent a more relevant model than orthotopic brain tumor xenograft models. However, it is challenging to implant microdialysis cannula in these animals because T2-weighted magnetic resonance imaging (MRI) does not show the reference point (bregma) traditionally used to obtain stereotactic coordinates. Thus, an alternative reference point that can be visualized on MRI images is needed. In this study, a novel reference point, identified as the intersection between the olfactory bulb/frontal lobe border and the midline between cerebral hemispheres on T2-weighted MRI images, was used to calculate anterior–posterior and medial–lateral coordinates of brain tumors in a GEMM. This point overlies a visible crossover between the rostral rhinal vein and the midline suture on the mouse skull, allowing for the conversion of the MRI coordinates into surgical stereotactic coordinates. Postmortem MRI and histological examination confirmed accurate probe placement. This procedure will facilitate the accurate and precise implantation of microdialysis probes for the study of anticancer drug penetration in brain tumors of GEMMs. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4210–4214, 2011

A modified surgical procedure is described to implant a microdialysis probe to sample ventricular cerebrospinal fluid (vCSF) in FVB mice. Microdialysis sampling of drugs in vCSF provides insight into drug penetration into the brain across the blood brain barrier (BBB) and the blood CSF barrier (BCB); however, this method has been reported primarily in larger animal species. Implanting a microdialysis probe in the lateral ventricle of a mouse is technically very challenging. The modification consisted of changes in the stereotaxic coordinates and insertion of the cannula and ultimately the probe at a 20 degrees angle. Exact placement of the probe was confirmed using ultrasound (US), micro-computed tomography (CT), and histologic review of serial paraffin sections. Additionally, studies of topotecan CSF penetration in the FVB mouse were conducted. With this modified procedure, the ventricular CSF to plasma AUC ratio of unbound topotecan lactone was greater than that previously reported using conventional methods. We speculate this is due to changes incorporated by the modified procedure that places the probe directly into the lateral ventricle allowing sampling of that discrete compartment. Thus, we propose that this modified procedure for placement of the microdialysis probe is superior to the conventional perpendicular method previously reported.