title: Intrathoracic organ injury associated with photodynamic therapy.
abstract: Photodynamic therapy has been proposed as a new modality for the local treatment of neoplasms limited to the pleural surface. Clinical use of photodynamic therapy will involve exposure of large surface areas of normal intrathoracic organs to tumoricidal doses of photodynamic therapy. This study details the pathologic changes that occur within the lung, heart, trachea, and diaphragm of Sprague-Dawley rats after administration of tumoricidal photodynamic therapy. Animals were injected with the photosensitizer Photofrin-II (Quadralogic Technologies, Vancouver, B.C., Canada), 10 mg/kg intraperitoneally, 24 hours before surface illumination of a portion of the target organ with gold vapor laser light (628 nm) (124 joules/cm2). Control animals were treated with light alone. After endotracheal intubation and mechanical ventilation, the lung and heart were exposed via left thoracotomy. The trachea was dissected in the neck, and the diaphragm was visualized via celiotomy. One site was treated per animal. Animals were killed at 24 hours, 48 hours, 72 hours, 1 week, 1 months, and 6 months after therapy. Histologic injury was numerically assessed by a single observer blinded to treatment and time of organ harvest. The Wilcoxon matched-pair signed-rank test was used to determine the statistical significance of differences between treated and control groups. Twenty-four hours after treatment the lung, heart, and trachea of rats subjected to photodynamic therapy demonstrated parenchymal injury (p less than 0.05). The diaphragm showed delayed injury 72 hours after therapy (p less than 0.05). Microscopic pulmonary changes included alveolar and endothelial disruption, intraalveolar hemorrhage, and fibrin deposition. Coagulation necrosis of myocardial fibers extending through the epicardium to involve up to 50% of myocardial thickness was observed. The diaphragm showed mesothelial hyperplasia with necrosis of superficial skeletal muscle. No similar gross or microscopic changes were present in the organs of control animals, or more than 48 hours after treatment in the trachea of animals that received photodynamic therapy. Photodynamic therapy induces a spectrum of tissue-specific injury, which may affect its usefulness in subsequent clinical trials.
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA 19111.
authors.forename: J J
authors.initials: JJ
authors.lastname: Pelton
authors.forename: M J
authors.initials: MJ
authors.lastname: Kowalyshyn
authors.forename: S M
authors.initials: SM
authors.lastname: Keller
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000473:pathology; D006321:Heart / Q000187:drug effects*; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000009:adverse effects; D007834:Lasers / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010778:Photochemotherapy / Q000009:adverse effects*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000473:pathology
chemical_list: D006415:Hematoporphyrins; D011838:Radiation-Sensitizing Agents; D017324:Hematoporphyrin Derivative