PHOTOFRIN-MEDIATED PHOTODYNAMIC THERAPY OF RAT PALATAL MUCOSA - NORMAL TISSUE EFFECTS AND LIGHT DOSIMETRY

Photodynamic therapy (PDT) is a treatment modality with potential appl ication far premalignant lesions and squamous cell carcinoma of the or al mucosa. PDT in principle has dual selectivity. This may result from a 'preferential' retention of the photosensitizer in target tissue. I n addition, the photodynamic activity will be limited to the irradiate d area because PDT will not affect tissues in the absence of excitatio n light, The specificity of PDT is limited by the fact that normal tis sues also retain the photosensitizer to some degree, which makes these tissues susceptible to PDT damage, To optimize PDT for oral malignanc ies, a study was undertaken on normal tissue to investigate the respon ses in rat palatal mucosa and surrounding anatomical structures. Eight y male Wistar rats were used in the study, Photofrin was administered i.v. at four doses (0, 2.5, 5 or 10 mg kg(-1) body weight). Irradiatio n for PDT was performed 24 h later. An argon pumped dye laser system w as used to produce light of two different treatment wavelengths (514.5 and 625 nm), and various energy density levels (0, 25, 50, 100 or 200 J cm(-2)). Early effects of PDT were studied at 2 days and late effec ts at 2 months after treatment. Twenty-four hours after i.v. administr ation of Photofrin, it was found that PDT affects normal tissues of th e oral cavity both macroscopically and microscopically. Combinations o f photosensitizer doses greater than or equal to 5 mg kg(-1) and light doses greater than or equal to 100 J cm(-2) caused severe and permane nt damage to the palatal mucosa and adjacent normal structures such as palatal bone and dentition.Light scattering and internal reflection u sually raise the fluence rate in tissue above the irradiance of the in cident beam. In an additional study using six male Wistar rats, the en ergy fluence rate at two treatment wavelengths (514.5 and 625 nm) was measured ex vivo in the palatal mucosa and adjacent anatomical structu res. As expected, the energy fluence rates were wave-length, tissue an d depth dependent. At the air-mucosa boundary, light of 625 nm was fou nd to have a three-times higher fluence rate than the primary incident beam. Under similar conditions, the fluence rate of 514.5 nm was foun d to be less, but still twice as high as the primary incident beam. At deeper levels of the rat maxilla, fluence rates were still elevated c ompared with the incident beam. For 625 nm light, this phenomenon was observed up to the level of the nasal cavity. These increased fluence rates could largely explain the pattern of damage to normal mucosa and surrounding anatomical structures.