Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC.
OBJECTIVE
Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC).


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.
Krueger
Thorsten
T
Department of Surgery, University Hospital of Lausanne, CH-1011 Lausanne. thorsten.krueger@chuv.hospvd.ch
Altermatt
Hans J
HJ
Mettler
Daniel
D
Scholl
Beatrix
B
Magnusson
Lennart
L
Ris
Hans-Beat
HB
D000818:Animals; D003199:Computer Systems; D004195:Disease Models, Animal; D005260:Female; D008652:Mesoporphyrins / Q000627:therapeutic use*; D008654:Mesothelioma / Q000188:drug therapy* / Q000601:surgery; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000295:instrumentation* / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011013:Pneumonectomy; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011874:Radiometry
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin