3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

Area of Science:

• Oncology
• Analytical Chemistry
• Pharmacology

Background:

• Mass Spectrometry Imaging (MSI) is a 2D technique for compound distribution in tissues.
• Absolute drug quantification using MSI is an emerging challenge.
• Malignant Pleural Mesothelioma (MPM) is a heterogeneous, drug-resistant cancer.

Purpose of the Study:

• To develop a 3D pipeline for studying drug penetration in tumors using MSI.
• To establish a novel drug quantification method by Matrix-Assisted Laser Desorption/Ionization (MALDI) MSI.
• To assess Paclitaxel (PTX) distribution and concentration in a 3D MPM model.

Main Methods:

• Developed a 3D computational reconstruction pipeline from 2D MSI data.
• Applied MALDI MSI to measure PTX distribution and concentration in MPM tumors.
• Utilized an internal standard for quantitative accuracy, comparable to HPLC.
• Analyzed drug penetration and concentration within different tumor sub-volumes.

Main Results:

• The 3D model accurately described PTX penetration in MPM, highlighting intratumoral heterogeneity.
• Significant portions of the tumor were found to be largely unreached by the drug.
• Quantitative results using the 3D MSI method showed good agreement with HPLC.
• Drug distribution varied considerably due to the complex tumor microenvironment.

Conclusions:

• 3D MSI provides crucial insights into drug concentration within tumor sub-volumes.
• Poor drug penetration suggests 'pseudo-resistance' as a factor in therapy ineffectiveness and tumor relapse.
• This 3D approach enhances understanding of drug delivery in heterogeneous solid tumors.