5th February 2019

Aptamer Group recently collaborated with a commercial partner to develop aptamers to a variety of small molecule drugs and their active metabolites for biosensor based therapeutic drug monitoring.  Therapeutic drug monitoring (TDM) is the clinical practice of measuring drugs and their subsequent metabolites at designated intervals to understand concentration in a patient’s bloodstream to optimize individual dosage regimens.

Irinotecan is a commercially available small molecule used to treat colon and small cell lung cancers. In the body, Irinotecan is activated to a therapeutically active metabolite 7-Ethyl-10-hydroxy-camptothecin (SN-38) which inhibits both DNA replication and transcription and the less effective metabolite aminopentane carboxylic acid (APC)  Monitoring of the level of both Irinotecan and metabolite SN-38 in human plasma is important to maximize therapeutic efficacy and monitor potential toxicity   Using our proprietary automated selection approach we were able select a set of aptamers which enable therapeutic monitoring of both Irinotecan and metabolite SN-38.

After successful selection of aptamers they were further tested to bind Irinotecan, APC and SN-38 in Biolayer Interferometry (BLI) Assays and ELISA like assays in varying amounts of plasma.

The BLI assay of an Irinotecan specific aptamer (CP13) from the selection in Graph 1 show specific binding to target drug in the therapeutic relevant concentration range and not negative target or SN-38 .

Irinotecan specific aptamer CP13 and an aptamer that binds both Irinotecan and SN-38 (CP11) were evaluated in a modified ELISA format in human plasma. Streptavidin plates with immobilised aptamers were incubated with a gradient of target and metabolites at therapeutically relevant concentrations and fluorescence was measured.  After background data was subtracted the results were plotted as fluorescence against target concentration in Graph 2.  CP13 demonstrates specificity to Irinotecan and not SN-38 whereas CP11 effectively measures both, allowing for determination of the ratio between Irinotecan and its active metabolite SN-38.

Graph 2: CP13 and CP11 aptamer binding selectivity in plasma ELISA like assay.

Conclusion:

Aptamers selected to Irinotecan and metabolites demonstrate specificity in BLI and ELISA like assays and utility for use in clinical drug monitoring assays. These aptamers and others will be available soon as part of our validated catalogue.

Follow up your interest in small molecule discovery and analysis and our new catalog by completing the form below.

Contact