For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

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

TitleA Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an [F]-Positron Emitting, Fluorescent Derivative of Dasatinib.
Publication TypeJournal Article
Year of Publication2017
AuthorsWang M, Kommidi H, Tosi U, Guo H, Zhou Z, Schweitzer ME, Wu LY, Singh R, Hou S, Law B, Ting R, Souweidane MM
JournalMol Cancer Ther
Volume16
Issue12
Pagination2902-2912
Date Published2017 Dec
ISSN1538-8514
KeywordsAnimals, Antineoplastic Agents, Brain Stem Neoplasms, Computer Systems, Dasatinib, Disease Models, Animal, Drug Delivery Systems, Glioma, Mice, Positron Emission Tomography Computed Tomography
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 ([F]-) so that F-positron emission tomography (PET) and fluorescent imaging can both be used to observe drug delivery to murine orthotopic glioma. Western blotting, binding studies (IC = 22 ± 5 nmol/L), and cell viability assays (IC = 46 ± 30 nmol/L) confirm nanomolar, effectiveness of [F]-, a dasatinib derivative that is visible by F-PET and fluorescence. [F]- 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. .

DOI10.1158/1535-7163.MCT-17-0423
Alternate JournalMol Cancer Ther
PubMed ID28978723
PubMed Central IDPMC6287766
Grant ListK99 EB013904 / EB / NIBIB NIH HHS / United States
R00 EB013904 / EB / NIBIB NIH HHS / United States