EXPERIMENTAL ASSESSMENT OF PHOTODYNAMIC THERAPY WITH CHLORINS FOR MALIGNANT MESOTHELIOMA

Objective: Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on i ntrathoracic tissues of minipigs with the same drug-light conditions t o optimise the antitumour activity of PDT while preventing photosensit ising injury to normal tissues, Methods: Laser light (20 J/cm(2)) at 6 52 nm was delivered to the xenografts 1-4 days after i.p. administrati on of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar d ose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respective ly. The extent of tumour necrosis was assessed by histomorphometry. In traoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-ligh t intervals ranging from 12 h to 6 days after i.v. administration of m THPC and pegylated mTHPC, respectively. Results: Both, mTHPC and pegyl ated mTHPC, resulted in photosensitised necrosis of mesothelioma xenog rafts at drug-light intervals from 1 to 4 days but the extent of necro sis was significantly larger by use of pegylated mTHPC instead of mTHP C at a drug-light interval of 3 and 4 days. The optimal tumourcidal ef fect was achieved with pegylated mTHPC at a drug-light interval of 4 d ays. 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 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. Conclusions: PDT w ith pegylated mTHPC reveals the potential of selective tumour destruct ion in this experimental setting and deserves further evaluation for i ntraoperative application in patients with malignant mesothelioma. (C) 1997 Elsevier Science B.V.