In order for an anticancer drug to be effective, it must gain access to solid tumors via the blood supply and penetrate the extravascular space to reach all of the cancer cells in sufficient concentration for therapeutic effect. These issues are magnified in the treatment of glioblastoma multiform (GBM) due to the added requirement of the drug to successfully pass the blood brain barrier (BBB). Drug delivery systems in the form of nanoparticles or antibody-drug conjugates, have been developed to address the difficulty in delivering sufficient drug concentrations to all target cells in solid tumors. However, detailed localization of the drug following NP delivery is challenging, as current vi...

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In order for an anticancer drug to be effective, it must gain access to solid tumors via the blood supply and penetrate the extravascular space to reach all of the cancer cells in sufficient concentration for therapeutic effect. These issues are magnified in the treatment of glioblastoma multiform (GBM) due to the added requirement of the drug to successfully pass the blood brain barrier (BBB). Drug delivery systems in the form of nanoparticles or antibody-drug conjugates, have been developed to address the difficulty in delivering sufficient drug concentrations to all target cells in solid tumors. However, detailed localization of the drug following NP delivery is challenging, as current visualization methods focus on imaging the labeled carrier (NP), but do not reveal the precise localization of the payload drug or its metabolites. This is unacceptable as drugs may diffuse or be transported significant distances from the NP into cancer cells at killing concentrations (desirable), or accumulate toxically in non-tumor cells (undesirable). The objective of this high-impact/high-risk CPRIT proposal is to develop an imaging method enabling free drug to be visualized alongside the delivery agent at high spatial detail within tumors. We propose a novel, innovative combinatorial approach using mass spectrometry imaging and imaging mass cytometry (MSI-IMC) to visualize free drug, metabolites, the NP delivery system, and biomarkers of cell damage and therapeutic response at extremely high resolution within a single tissue section. The developed technique will be high reward as it will provide crucial drug localization information for optimizing NP design and minimizing costly drug development attrition. Furthermore, our single-section imaging technique will minimize the amount of tissue required, opening up potential clinical applications for drug and therapeutic response monitoring in small core biopsies of many different tumor types.

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