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Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium

Brain Tumor Center, Massachusetts General Hospital, Boston, MA 02114 (R.K.B., F.H.H.); National Cancer Institute, Bethesda, MD 20892 (E.F.); National Institutes of Health, Bethesda, MD 20892 (P.M.B); Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455 (W.F.E.); St. Jude Children's Research Hospital, Memphis, TN 38105 (C.F.S.); Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111 (J.M.G.); Laboratory of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857 (J.M.C.); CMA Microdialysis, North Chelmsford, MA 01863 (R.P.P); The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 (J.F.D.); Human Performance Laboratory, East Carolina University, Greenville, NC 27858 (R.C.H.); Psychiatry Department, Yale University, New Haven, CT 06519 (I.C.); Department of Neuro-Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231 (S.A.G.); Department of Medicine, Duke University Medical Center, Durham, NC 27710 (O.M.C.); USA

¹ Address correspondence to Ramsis K. Benjamin, Carolina Neurosurgery & Spine Associates, Neuro-Oncology Center, 1628 E. Morehead Road, Suite 200, Charlotte, NC 28207 (Ramsis.benjamin{at}cnsa.com).

Abstract

In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials.

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