Mass Spectrometry Imaging as a powerful tool to go beyond systemic exposure and to understand PK and tissue distribution of an anti-cancer prodrug (CBR-T01).
Thursday 4th of June
9.00 am Boston Time
3.00 pm French Time
Mathieu Gaudin1, Andrea Casazza2, Nicolas Vossart1, Anthony Dessaux1, Juliette Masure1, Raphaël Legouffe1, Jonathan Stauber3, Olivier Defert2, David Bonnel1 and Nele Kindt2
1: ImaBiotech SAS, Parc Eurasanté, 152 Rue du Dr Yersin, 59120 Loos, France
2: CoBioRes, Herestraat 49, Box 913, 3000 Leuven, Belgium
3: ImaBiotech Corp, 44 Manning Road Suite 105, Billerica, MA 01821, USA
Going beyond conventional PK determination in order to understand drug pharmacokinetics at the tissue level is of utmost interest for the development of safe and efficient drugs. Mass Spectrometry Imaging of whole-body tumor-bearing mice provides an efficient experimental setting to achieve comprehensive characterisation of drug pharmacokinetics at an early stage for better and faster drug candidate selection.
Since designing prodrugs can be an effective way toward better PK properties, more targeted efficacy and lower adverse effects, the ability of Mass Spectrometry Imaging to discriminate drug and metabolites gives a competitive advantage over classical methods (LC-MS/MS and Quantitative Whole-Body Autoradiography) for performing the early evaluation of the distribution and exposure of a prodrug.
In this webinar, the added-value of this label-free methodology is illustrated by the comparative investigation of the plasma PK and tumor cells exposure of a chemotherapeutic prodrug showing the targeted delivery of activated drug to the tumor microenvironment while decreasing undesirable tissue exposure to cytotoxic molecules. The prodrug developed by CoBioRes takes advantage of selective enzymes present in the tumor microenviroment that convert the prodrug into a potent cytotoxic agent. The prodrug approach enables tumor-targeted drug release and reduction of systemic toxicity of chemotherapeutics in preclinical models. The Mass Spectrometry Imaging approach allowed to show the improved safety profile of the prodrug in preclinical models compared to free cytotoxic drug.