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Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC
Thorsten Krueger1, Hans J Altermatt, Daniel Mettler
1Department of Surgery, University Hospital of Lausanne, CH-1011 Lausanne. thorsten.krueger@chuv.hospvd.ch
Background And Objectives:
Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC).
Study Design/Materials And Methods:
(a) PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 J/cm(2); 0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b) Intraoperative PDT with similar treatment conditions was performed in the chest cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an optical integrating balloon device combined with in situ light dosimetry.
Results:
(a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than in untreated tumors (P < or = 0.01) without causing damage to normal tissue. (b) Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean fluence and fluence rates measured at four sites of the chest cavity ranged from 10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2) (mean +/- SD). Histology 3 months after light delivery revealed no PDT related tissue injury in all but one animal.
Conclusions:
PEG-mTHPC mediated PDT showed selective destruction of mesothelioma xenografts without causing damage to intrathoracic organs in pigs at similar treatment conditions. The light delivery system afforded regular light distribution to different parts of the chest cavity.
Insights
Photodynamic therapy (PDT) with PEG-mTHPC selectively destroyed malignant pleural mesothelioma xenografts without harming normal tissues. Intraoperative PDT in pigs was well-tolerated, showing promise for mesothelioma treatment.
Area of Science:
- Oncology
- Photochemistry
- Surgical Innovation
Background:
- Malignant pleural mesothelioma is an aggressive cancer with limited treatment options.
- Photodynamic therapy (PDT) offers a targeted approach to cancer treatment.
- A novel polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC) was developed for PDT.
Purpose of the Study:
- To experimentally assess the efficacy and safety of PEG-mTHPC mediated PDT for malignant pleural mesothelioma.
- To evaluate intraoperative PDT in a preclinical porcine model following extrapleural pneumonectomy (EPP).
Main Methods:
- PDT was tested on H-meso-1 xenografts using a 652 nm laser and varying doses of PEG-mTHPC.
- Intraoperative PDT was performed in the chest cavity of minipigs post-EPP using a specialized light delivery device and dosimetry.
- Tumor response and tissue damage were assessed via histology.
Main Results:
- PEG-mTHPC mediated PDT significantly increased tumor necrosis in xenografts compared to controls (P < or = 0.01).
- No damage to normal tissue was observed in xenograft studies.
- Intraoperative PDT in pigs was well-tolerated in 17 of 18 animals, with no significant PDT-related tissue injury observed at 3 months post-treatment.
Conclusions:
- PEG-mTHPC mediated PDT demonstrates selective destruction of mesothelioma xenografts.
- Intraoperative PDT in a porcine model showed safety and effective light distribution within the chest cavity.
- This approach holds potential for treating malignant pleural mesothelioma.