Endobronchial photodynamic therapy: comparison of mTHPC and polyethylene glycol-derived mTHPC on human tumor xenografts and tumor-free bronchi of minipigs.
OBJECTIVE
Photodynamic therapy (PDT) with mTHPC and polyethylene glycol-derived mTHPC (pegylated mTHPC) was compared on nude mice bearing human squamous cell carcinoma and adenocarcinoma xenografts. The same treatment regimens were applied to the bronchi of tumor-free minipigs to assess injury to normal tissue.


METHODS
Laser light (652 nm, 20 J/cm2) was delivered as surface radiation to the xenografts 4 days after intraperitoneal administration of 0.1 mg/kg mTHPC or an equimolar dose of pegylated mTHPC, respectively. The extent of tumor necrosis was assessed by histomorphometry. Endobronchial PDT was performed on the bronchi of minipigs with the same drug and light doses at drug-light intervals ranging from 12-96 hr.


RESULTS
Both sensitizers produced larger necrosis of squamous cell carcinoma and adenocarcinoma xenografts than was observed in untreated controls (P < 0.005). Pegylated mTHPC led to larger tumor necrosis than mTHPC in squamous cell carcinoma (P < 0.001), but not in adenocarcinoma xenografts. mTHPC-PDT resulted in ulceration and necrosis of bronchial mucosa in minipigs at drug-light intervals ranging from 12-48 hr, which was not observed after use of pegylated mTHPC.


CONCLUSIONS
In this setting, pegylated mTHPC had advantages as a photosensitiser compared to mTHPC.
Department of Thoracic and Cardiovascular Surgery, University of Berne, Switzerland.
H B
HB
Ris
V
V
Im Hof
C M
CM
Stewart
D
D
Mettler
H J
HJ
Altermatt
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001984:Bronchial Neoplasms / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D006801:Humans; D008652:Mesoporphyrins / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin