The cancer drug Taxol (paclitaxel) is very unevenly distributed in a model of malignant pleural mesothelioma, according to a new imaging technique that visualizes how a drug spreads within a tumor. This method may help researchers understand why mesothelioma treatment often fails, and help develop approaches that maximize drug uptake and distribution in tumors.
The study, “Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging,” appeared in the journal Scientific Reports.
In healthy tissue, it is assumed that the concentration of a drug in the blood is in equilibrium with the levels in tissue. Because of the unique properties of tumors, this may not necessarily be true with cancer, in which differences in physicochemical properties, blood flow, and inflammation may all contribute to uneven uptake of a drug into the tissue.
Researchers at Italy’s Mario Negri Institute for Pharmacological Research developed a method, using mass spectrometry imaging, to visualize the presence of a drug molecule within the tumor. This lets them measure both the parent drug and its metabolites at the same time, and also examine the tumor structures where the drug accumulates or is absent.
Using mice with various tumors, the research team showed that Taxol is more unevenly distributed in mesothelioma than in ovarian, breast cancer and other tumors. The mesothelioma cells were initially isolated from a patient, and the tumor is very similar to that originally described in the patient.
Analyses showed patches with relatively high concentrations of Taxol, and areas with nearly no drug present.
Variations in distribution were not mirrored by the total levels of the drug, measured using a standard analysis of a whole tumor tissue, the team found. Further analyses seemed to indicate that the tissue architecture influenced the spread of the drug, with areas with cell death or fibrosis showing reduced drug uptake.
While the method can be used to better understand why mesothelioma is so difficult to treat, it can also be used to assess approaches to boost drug distribution in tumors.