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The blood brain barrier can limit the efficacy of systemically delivered drugs in treating neurological malignancies; therefore, alternate routes of drug administration must be considered. The Abl-kinase inhibitor, dasatinib, is modified to give compound 1 ([ 18 F]- 1 ) so that 18 F-positron emission tomography (PET) and fluorescent imaging can both be used to observe drug delivery to murine orthotopic glioma. In vitro Western blotting, binding studies (IC 50 = 22 ± 5 nmol/L), and cell viability assays (IC 50 = 46 ± 30 nmol/L) confirm nanomolar, in vitro effectiveness of [ 18 F]- 1 , a dasatinib derivative that is visible by 18 F-PET and fluorescence. [ 18 F]- 1 is used to image dynamic direct drug delivery via two different drug delivery techniques to orthotopic murine brainstem glioma (mBSG) bearing mice. Convection enhanced delivery (CED) delivers higher concentrations of drug to glioma-containing volumes versus systemic, tail-vein delivery. Accurate delivery and clearance data pertaining to dasatinib are observed, providing personalized information that is important in dosimetry and redosing. Cases of missed drug delivery are immediately recognized by PET/CT, allowing for prompt intervention in the case of missed delivery. Mol Cancer Ther; 16(12); 2902-12. ©2017 AACR .

molecular cancer therapeutics

A Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an 18[F]-Positron Emitting, Fluorescent Derivative of Dasatinib