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Updated: May 20, 2026
Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
Extracellular protease imaging for cell mass tracking of xenografted human malignant pleural mesothelioma
Lanlan Zhou1, Wafik El-Deiry, Wenge Wang
1Department of Medicine (Hematology/Oncology), Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Penn State College of Medicine, Penn State Hershey Cancer Institute, Penn State Hershey Medical Center, Hershey, PA, USA.
Abstract:
Malignant pleural mesothelioma (MPM) is locally aggressive and challenging to quantitate non-invasively in vivo, particularly in orthotopic models of disease. We describe imaging of extracellular protease activity, typically elevated in locally aggressive tumors, as a novel method for tracking MPM in vivo. Mice bearing human MPM subcutaneous flank xenografted tumors were imaged with ProSense 680, an optical imaging agent of extracellular cysteine protease activity. The relative contribution of extracellular cysteine proteases to the ProSense tumor signal was estimated using RT-PCR quantitation of cysteine protease RNA expression of the MPM cell lines and compared to ArrayExpress microarray RNA expression data from human MPM tumors. Feasibility of orthotopic intraperitoneal MPM cell mass tracking with fluorescence signal was evaluated using CellVue Maroon-coated MSTO-211H and compared to bioluminescent signal using luciferase-transfected MSTO-211H cells. ProSense 680 yielded a robust tumor signal in MPM subcutaneous grafts, primarily resulting from MPM secretion of cathepsin L demonstrated not only by RT-PCR data on MPM cell lines but also by microarray expression data from resected human patient tumors. CellVue Maroon intraperitoneal tumor signal was robust and durable indicating feasibility of intraperitoneal cell mass tracking of orthotopically-xenografted MPM. Optical imaging of extracellular cysteine protease activity is useful for tracking MPM tumor cell mass in vivo. Intraperitoneal MPM cell mass tracking of fluorescently labeled tumor is feasible.
Insights
Optical imaging tracks malignant pleural mesothelioma (MPM) progression in vivo. This novel method visualizes extracellular protease activity, aiding in non-invasive tumor monitoring and assessment of therapeutic efficacy.
Area of Science:
- Oncology
- Medical Imaging
- Biochemistry
Background:
- Malignant pleural mesothelioma (MPM) is a locally aggressive cancer.
- Non-invasive in vivo quantification of MPM, especially in orthotopic models, remains challenging.
- Extracellular protease activity is often elevated in aggressive tumors.
Purpose of the Study:
- To develop and evaluate novel optical imaging methods for tracking MPM in vivo.
- To assess extracellular protease activity as a biomarker for MPM.
- To determine the feasibility of tracking orthotopic MPM models.
Main Methods:
- Mice bearing subcutaneous MPM xenografts were imaged using ProSense 680, an optical agent for extracellular cysteine protease activity.
- RT-PCR and microarray data were used to quantify cysteine protease RNA expression in MPM cell lines and human tumors.
- Orthotopic MPM models were tracked using fluorescently labeled cells (CellVue Maroon) and compared to bioluminescent imaging.
Main Results:
- ProSense 680 provided a robust signal in subcutaneous MPM grafts, mainly due to cathepsin L secretion by MPM.
- RT-PCR and human tumor microarray data confirmed cathepsin L's contribution to the signal.
- Fluorescently labeled intraperitoneal MPM demonstrated robust and durable signal, confirming feasibility for orthotopic tracking.
Conclusions:
- Optical imaging of extracellular cysteine protease activity is a viable method for tracking MPM tumor burden in vivo.
- Fluorescent labeling enables feasible tracking of intraperitoneal MPM cell mass in orthotopic models.
- This approach offers a novel non-invasive tool for MPM research and potentially clinical monitoring.
