Intraoperative photodynamic therapy of the chest cavity in malignant pleural mesothelioma bearing rats.
OBJECTIVE
Experimental assessment of anticancer effect, normal tissue damage, and toxicity of intrathoracic mTHPC-mediated photodynamic therapy (PDT) combined to surgery in malignant pleural mesothelioma (MPM) bearing rats.


METHODS
Six days after implantation of syngenic malignant mesothelioma cells in the left chest cavity of Fischer rats (n = 21) and 4 days after sensitization (0.1 mg/kg mTHPC), a left-sided pneumonectomy was performed, followed by intraoperative light delivery (652 nm, fluence 20 J/cm(2)), either by spherical illumination of the chest cavity (fluence rate 15 mW/cm(2)) or by focal illumination of a tumor area (fluence rate 150 mW/cm(2)). Controls comprised tumor-bearing untreated animals, tumor-bearing animals undergoing pneumonectomy, and tumor-bearing animals undergoing pneumonectomy and light delivery without sensitization or sensitization without light delivery. No thoracocentesis was performed during follow-up.


RESULTS
An invasively growing sarcomatous type of mesothelioma was found in all animals at day 10, without tumor necrosis in control animals. PDT resulted in 0.5-1 mm deep inhomogeneous tumor necrosis after spherical, and in a 1-2 mm deep tumor necrosis after focal illumination. No injury to mediastinal organs was observed, neither after PDT with spherical nor with focal light delivery except focal interstitial lung fibrosis at the mediastinal area of the opposite lung. All animals with pneumonectomy followed by spherical PDT of the entire tumor-bearing chest cavity died within 72 hours whereas all other animals survived. All animals that died presented massive pleural effusion.


CONCLUSIONS
PDT following pneumonectomy in mesothelioma bearing rats was technically feasible and allowed to study its effect on tumor and normal tissues. PDT-related tumor necrosis was observed after spherical and focal light delivery, however, pneumonectomy followed by PDT with spherical light delivery to the tumor-bearing chest cavity resulted in fatal complications.
Krueger
Thorsten
T
Thoracic Surgery Unit, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland. thorsten.krueger@chuv.hospvd.ch
Pan
Youmin
Y
Tran
Nam
N
Altermatt
Hans-Joerg
HJ
Opitz
Isabelle
I
Ris
Hans-Beat
HB
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D007432:Intraoperative Period; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use; D008654:Mesothelioma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D011013:Pneumonectomy; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin