PHOTODYNAMIC THERAPY WITHIN EDEMATOUS BRAIN-TISSUE - CONSIDERATIONS ON SENSITIZER DOSE AND TIME POINT OF LASER IRRADIATION

Photosensitizer is known to spread with vasogenic edema fluid arising from a cerebral lesion (Neurosurg 33:1075-1082, 1993), which may be es sential for sensitizing malignant cells outside the main tumor mass. T he present experiments seek to elucidate whether resultant necrosis of perifocal brain tissue after laser irradiation follows a correspondin g time pattern and whether damage depends on the photosensitizer dose. Male Wistar rats were anaesthetized with chloralhydrate for venous ca nnulation, craniotomy and focal cold lesion in order to induce vasogen ic edema. Simultaneously, Photofrin IIR (PF II) was administered at a dose of 5 mg kg(-1). The animals were re-anaesthetized after either 4, 12 or 24 h for the irradiation of lesion and perifocal tissue with 20 0 J cm(-2) of laser light (630 nm). The brains of other animals were i rradiated 4 h after cold lesion with 200 J cm(-2) after receiving eith er 0, 2.5 or 5 mg kg(-1) PF II (all groups: n=6). Resultant necrosis w as assessed planimetrically in serial coronal cryosections of brains p erfusion fixed 24 h after irradiation. Necrosis was significantly enha nced with irradiation 4 h after cold lesion and photosensitizer (avg. area +/-SD: 4.3 +/- 0.7 mm(2)) compared with lesion only (0.84 +/- 0.2 mm(2)). Maximal necrosis (6.3 +/- 1.6 mm(2)) occurred with irradiatio n 12 h after lesion, whereas necrosis was only slightly increased with irradiation at 24 h (2.8 +/- 0.4 mm(2)). Furthermore, the area of nec rosis was dependent on the sensitizer dose (0 mg kg(-1): 0.7 +/- 0.3 m m(2), 2.5 mg kg(-1): 2.09 +/- 0.2 mm(2), 5 mg kg(-1): 4.3 +/- 0.7 mm(2 ); all differences p < 0.05). Therefore, to prevent unwanted side-effe cts such as necrosis of edematous but otherwise healthy, peritumoral t issue in the treatment of malignant cerebral tumors by PDT, tribute sh ould be paid to the possibility of time and dose dependent sensitizati on of the perifocal tissue after i.v. administration of photosensitize r.