Cerebral microdialysis sampling is used to monitor CNS anti-cancer drug disposition in mouse models1,2
. This approach provides advantages over other sampling methods (e.g., whole tissue homogenization) including sampling from discrete anatomic compartments such as the brain extracellular fluid (ECF) or ventricular cerebrospinal fluid (vCSF)3
, sampling from normal brain or brain tumor tissue, and acquisition of unbound or pharmacologically active drug moieties4
. Furthermore, microdialysis enables serial sampling from individual animals, thereby reducing the number of animals required for pharmacokinetic investigations5
Microdialysis has been frequently employed in studying anti-cancer drug penetration within brain tumors, particularly high-grade gliomas 6–9
. These studies are most often performed using murine orthotopic xenograft models in which human glioma cells are stereotactically injected into a defined brain location and the microdialysis guide cannula is simultaneously implanted. Tumor tissue then develops and surrounds the cannula6–8
. Although orthotopic tumor xenograft models are easy to use, relatively inexpensive, and reproducible, in many cases the genetics and histology of human tumors are not adequately recapitulated10
. In addition, the tumor microenvironment and host immune responses are likely altered in immunodeficient mice, which diminish the ability of xenograft models to truly recapitulate the features observed in human tumors11
. In contrast, genetically engineered murine models (GEMMs) of brain tumors bestow many of the genetic and histological features of malignant human brain tumors11
. In general, these mouse models develop tumors spontaneously upon alteration of signaling pathways critical for the development of the specific tumor of interest11,12
. Thus, molecular and other complex processes including specific contributions of the tissue microenvironment, such as tumor angiogenesis, can appropriately mimic human disease in these spontaneous tumor models.
In GEMMs, heterogeneous tumor growth patterns and development of tumors in different brain regions pose several technical challenges to using these models for CNS pharmacokinetic investigations12
. For example, a major challenge to using cerebral microdialysis to study anti-cancer drug penetration in tumors of GEMMs is the difficulty of acquiring stereotactic coordinates to accurately place a microdialysis cannula in the tumor. Traditionally, the coordinates of the intersection of the coronal and sagittal sutures (bregma point) are used as a reference point for the placement of the microdialysis cannula3,13
. However, this approach is not practical in GEMMs because the bregma does not appear on images derived by MRI, which is the imaging method used to identify the size and location of the spontaneously arising tumors in the brain. The objective of the current study was to use in vivo MRI imaging to identify a reference point for implanting microdialysis cannula in spontaneously arising tumors in a GEMM for high-grade glioma. The accuracy of cannula placement was verified by post-mortem MRI and histological examination.