Histone deacetylase (HDAC) inhibition is becoming an increasingly popular approach to treat cancer, as HDAC overexpression is common in many malignancies. The blood-brain barrier (BBB) prevents systemically delivered drugs from reaching brain at effective concentration, making small-molecule-HDAC inhibition in brain tumors particularly challenging. To circumvent the BBB, novel routes for administering therapeutics are being considered in the clinic, and a need exists for drugs whose deliveries can be directly imaged, so that effective delivery across the BBB can be monitored. We report chemistry for radiolabeling the HDAC inhibitor, panobinostat, with fluoride-18 (compound-1). Like panobinostat, compound 1 retains nanomolar efficacy in diffuse intrinsic pontine glioma (DIPG IV and XIII) cells (IC50 = 122 and 108 nM, respectively), with lesser activity against U87 glioma. With a favorable therapeutic ratio, 1 is highly selective to glioma and demonstrates considerably less toxicity toward healthy astrocyte controls (IC50 = 5265 nM). Compound 1 is stable in aqueous solution at physiological pH (>7 days, fetal bovine serum), and its delivery can be imaged by positron emission tomography (PET). Compound 1 is synthesized in two steps, and employs rapid, late-stage aqueous isotopic exchange 18F-radiochemistry. PET is used to image the in vivo delivery of [18F]-1 to the murine central nervous system via convection enhanced delivery.