Journal
MOLECULAR CANCER THERAPEUTICS
Volume 16, Issue 12, Pages 2902-2912Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-17-0423
Keywords
-
Categories
Funding
- National Institute of Biomedical Imaging and Bioengineering [K99/R00EB013904]
- Alex Lemonade Stand Foundation for Childhood Cancer
- Alex Lemonade Stand Foundation Pediatric Oncology Student Training Program
- Matthew Larson Foundation for Pediatric Brain Tumors Research Grant
- St. Baldrick's Summer Fellow Grant
Ask authors/readers for more resources
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 ([F-18]-1) so that F-18-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 [F-18]-1, a dasatinib derivative that is visible by F-18-PET and fluorescence. [F-18]-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. (C) 2017 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available