Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC

• Published in: Lasers in surgery and medicine 2003-01, Vol.32 (1), p.61-68
• Main Authors: Krueger, Thorsten, Altermatt, Hans J., Mettler, Daniel, Scholl, Beatrix, Magnusson, Lennart, Ris, Hans-Beat
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Computer Systems; Disease Models, Animal; dosimetry; Female; Medical sciences; Mesoporphyrins - therapeutic use; Mesothelioma - drug therapy; Mesothelioma - surgery; Mice; Mice, Nude; mTHPC foscan; neoplasm; nude mice; pegylation; Photochemotherapy - instrumentation; Photochemotherapy - methods; photodynamic therapy; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - therapeutic use; pleura; pleural mesothelioma; Pleural Neoplasms - drug therapy; Pleural Neoplasms - surgery; Pneumology; Pneumonectomy; Polyethylene Glycols - therapeutic use; Radiometry; swine; thorax; Treatment with physical agents; Treatment. General aspects; Tumors; Tumors of the respiratory system and mediastinum; xenograft
• ISSN: 0196-8092; 1096-9101
• DOI: 10.1002/lsm.10113

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/cm2; 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 ≤ 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/cm2 and 5.5 ± 1.2 to 7.9 ± 1.7 mW/cm2 (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. Lasers Surg. Med. 32:61–68,2003. © 2003 Wiley‐Liss, Inc.