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

ABSTRACT: 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 ([¹⁸F]-1) so that ¹⁸F-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 (IC₅₀ = 22 ± 5 nmol/L), and cell viability assays (IC₅₀ = 46 ± 30 nmol/L) confirm nanomolar, in vitro effectiveness of [¹⁸F]-1, a dasatinib derivative that is visible by ¹⁸F-PET and fluorescence. [¹⁸F]-1 is used to image dynamic

SUBMITTER: Wang M 

PROVIDER: S-EPMC6287766 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature