PHOTODYNAMIC THERAPY

EXPERIMENT SHOWS SELECTIVE TUMOR DESTRUCTION POTENTIAL OF PHOTODYNAMIC THERAPY. Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on inner chest tissues of minipigs with the same drug-light conditions to optimize the antitumor activity of PDT while preventing photosensitising injury to normal tissues. Laser light was delivered to the xenografts after administration of m-tetrahydroxyphenyl-chlorin (mTHPC) or an equal dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed on the basis of microscopic anatomy. Intraoperative PDT was then performed to the chest cavity of minipigs by a sternotomy with the same drug-light conditions at drug-light intervals ranging from twelve hours to six days after i.v. administration of mTHPC and pegylated mTHPC, respectively. RESULTS: Both mTHPC and pegylated mTHPC resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from one to four days, but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of three and four days. The optimal tumorcidal effect was achieved with pegylated mTHPC at a drug-light interval of four days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of three days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. CONCLUSIONS: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma. Ris, et al., European Journal of Cardio-Thoracic Surgery, 12(4):542-8, October 1997. Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on inner chest tissues of minipigs with the same drug-light conditions to optimize the antitumor activity of PDT while preventing photosensitising injury to normal tissues. Laser light was delivered to the xenografts after administration of m-tetrahydroxyphenyl-chlorin (mTHPC) or an equal dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed on the basis of microscopic anatomy. Intraoperative PDT was then performed to the chest cavity of minipigs by a sternotomy with the same drug-light conditions at drug-light intervals ranging from twelve hours to six days after i.v. administration of mTHPC and pegylated mTHPC, respectively. RESULTS: Both mTHPC and pegylated mTHPC resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from one to four days, but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of three and four days. The optimal tumorcidal effect was achieved with pegylated mTHPC at a drug-light interval of four days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of three days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. CONCLUSIONS: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma. Ris, et al., European Journal of Cardio-Thoracic Surgery, 12(4):542-8, October 1997.

PHOTODYNAMIC THERAPY AS ADJUVANT THERAPY IN SURGICALLY TREATED PLEURAL MALIGNANCIES. Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical removal of the tumor followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The position of the light delivery fiber was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and and effusion of blood within the pericardium). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 hours after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with leukocyte cells and edema of the striated muscle cells. Of the five patients treated, four are alive with no signs of recurrent tumor, with a follow-up of nine to eleven months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (one hour). This protocol is well suited for adjuvant treatment with PDT in malignant pleural tumours. Baas, et al., British Journal of Cancer, 76(6):819-26, 1997.