What the “cellular level” can deliver in clinical trials?
From Plasma to cellular level
Matthew Rizk, Director (Quantitative Pharmacology & Pharmacometrics at Merck) published “exclusive use of plasma exposure in pharmacokinetic–pharmacodynamic (PK/PD) models may lead to suboptimal assessment of exposure–response relationships and inaccurate dose selection” (Clin Transl Sci. 2017 May, Importance Drug pharmacokinetics at the site of action).
Especially in heterogeneous tissue, it is key to understand how much drug reach the targeted cells and at the same time measure the activity. There are many reasons to expect off target affinity in human biopsies and we experienced a lot of lack of activity due to misinterpretation of drug concentration around tumor cells for example.
Measuring PK/PD of each cell for a deep PK/PD
We propose our services using large number of imaging techniques (Mass Spectrometry Imaging, MALDI imaging, Elemental imaging, High Multiplex ImmunoFluorescence, and other techniques) to localize and quantify your drugs and biomarkers at the same time and measure the ratio of drug/biomarker concentration at a cellular level.
- With these tools, we measure the drug distribution and concentration in biopsies
- We measure the level of exposure of the drugs in targeted cells
- We measure the activity and efficacy at a cellular level and measure the number of cells that responds to the therapy
- We measure the amount of targeted cells in the tissue
- We stratify the patients that respond to therapy regarding the amount of drug versus companion biomarkers.