Intratumoral microdialysis

Microdialysis is, to date, the only sampling technique used for continuous therapeutic drug or metabolite monitoring and assessment of surrogate markers for response (or toxicity) in theextracellular fluid of tissues. Thanks to its advantages over other existing methods, microdialysis in tumors is becoming more and more important and thus provides a means to serially sample the tumor extracellular fluid from which a concentration versus time-profile can be determined, with minimal tissue damage or fluid balance alteration. In addition, a single microdialysis probe allows evaluation of drug and intended analyte concentrations, for the determination of pharmacokinetic (PK) and pharmacodynamic (PD) analysis.

 Microdialysis as a tool for intra-tumoral analyte/drug concentration assessment

Using its valuable in vivo tumor models, Explicyte offers to run intra-tumoral microdialysis-based studies for the evaluation of therapeutic anti-cancer agents and/or surrogate markers for response to treatments.

Intratumoral microdialysis scheme

Schematic illustration of intra-tumoral microdialysis technique for tumor extracellular fluid sampling and analysis.

Our microdialysis platform has been used to evaluate levels of kynurenine as a marker of kynurenine pathway (KP) activation. The KP is initiated by IDO1/TDO2 enzymes known to promote tumor immune escape and resistance to standard immune checkpoint inhibitors (aCTLA-4, aPD-1, aPD-L1), thereby leading to the development of strategies targeting these enzymes in combination with immune checkpoint blockade.

Kynurenine Microdialysis

Determination of kynurenine levels in tumor dialysates. Balb/c mice were challenged with CT26 tumors either controls (Mock) or expressing IDO1. Tumor extracellular fluid was then sampled by microdialysis when the tumors reached 160-400mm3 (~ at day 21 after tumor cell inoculation), and kynurenine concentrations have been determined by immunoassay. The higher kynurenine concentration within IDO1-proficient CT26 tumors supports a stronger tryptophan degradation when compared to CT26_Mock counterparts.

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Using its valuable in vivo tumor models, Explicyte offers to run intra-tumoral microdialysis-based studies for the evaluation of therapeutic anti-cancer agents and/or surrogate markers for response to treatments.