As a proof of principle study, we have applied MALDI IMS in 3D cell culture systems to map the distribution of the clinically used therapeutic, irinotecan. The penetration of the drug into colon spheroids increases as a function of time. Three metabolites of irinotecan have also been visualized. Identification of these and other metabolites was confirmed with an LC-MS/MS study. This combination of 3D tumor models analyzed by MALDI IMS technology and LC-MS/MS analysis could assist to reduce animal testing, yield more predictive data, and reduce cost and time to efficiently evaluate new drug candidates as well as identifying their known and potential metabolites. All of these advantages would boost the speed of therapeutic development from lab to market. This system is also applicable to mapping drugs and metabolites in various diseases.
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