Microdialysis for dynamic changes of target molecules

Microdialysis is to date the only in vivo sampling technique used for continuous therapeutic drug or metabolite/analyte monitoring and assessment of surrogate markers for response and toxicity, in the extracellular fluid (ECF) of tissues. The use of this non/minimally invasive microdialysis-based methodology in tumors is relatively new and is becoming more and more important, to evaluate, for instance, tumor ECF disposition of anti-cancer agents and factors affecting delivery and removal of anti-cancer agents, gene therapy, angiogenesis inhibitors… Furthermore, intratumoral microdialysis is becoming an invaluable tool for the assessment of physiological and pathophysiological role of metabolic/signaling pathways involved in the tumor metabolism and tumor immune escape. Technically, intratumoral microdialysis allows for providing comprehensive means to serially sample the tumor ECF – with minimal tissue damage or fluid balance alteration - from which a concentration can be determined versus time-profile. In addition, a single microdialysis probe can simultaneously allow for sampling several analytes of interest, thereby enabling the evaluation of pharmacokinetic and pharmacodynamic changes.
A dedicated platform is thus available to run intratumoral microdialysis in valuable in vivo tumor models, and combined with suitable a detection method, for the evaluation of therapeutic anti-cancer agents and/or surrogate markers in response to treatments.
 

Principle & key advantages of microdialysis


Schematic illustration of intra-tumoral microdialysis technique for tumor extracellular fluid sampling and analysis.
  • Microdialysis allows measuring the release and metabolism of molecules / markers of interest diffusing in the ECF of the tumor.
  • Appropriate to assess physiological and pathophysiological role of metabolic and signaling pathways involved in the tumor metabolism.
  • Well-suited for PK and PD monitoring of drug and/or intended analyte levels, when combined to a suitable detection method.

Technical features of microdialysis platform

Microdialysis platform
Schematic illustration of in-house microdialysis platform

Schematic illustration of in-house microdialysis platform

Kynurenine recovery rate
Determination of Kynurenine recovery rate. CT26 colon tumor cells were cultured and supernatants were retrieved. Known concentrations of kynurenine were added for recovery determination, and 2 fractions have been collected by microdialysis (each fraction over 30min). Kynurenine concentrations were detected and measured by immunoassay.

Determination of Kynurenine recovery rate. CT26 colon tumor cells were cultured and supernatants ...

Kynurenine levels in tumor dialysates
Determination of kynurenine levels in tumor dialysates. Balb/c mice were challenged with CT26 tumors either WT (Mock) or expressing IDO-1. Tumor ECF was sampled by microdialysis when tumors reached 160-400mm3 (~at day 21 post-tumor cell inoculation), and kynurenine concentrations have been determined by immunoassay. The higher kynurenine concentration within IDO1-expressing CT26 tumors supports a stronger tryptophan degradation when compared to CT26-Mock tumors.

Determination of kynurenine levels in tumor dialysates. Balb/c mice were challenged with ...