5-AMINOLEVULINIC ACID-INDUCED ENDOGENOUS PORPHYRIN FLUORESCENCE IN 9LAND C6 BRAIN-TUMORS AND IN THE NORMAL RAT-BRAIN

A new approach in photodynamic therapy is the use of endogenous porphy rins for sensitisation of tumours to light. The induction of endogenou s porphyrins after intravenous injection of 5-amino-levulinic acid (AL A, 200 mg kg(-1)) was studied in 23 rats, bearing intracranial 9L or C 6 tumours. After 0, 2, 4, 6, 8, and 22 hours the rats were sacrificed and the fluorescence distribution of endogenous porphyrins was studied in brain tissue sections with a standard fluorescence microscope and a confocal laser scanning microscope. The role of blood-brain barrier disruption on porphyrin production was studied in 2 rats with a cryo-l esion of the cortex. Additionally, 9L and C6 tumour cell cultures were incubated with ALA for 8 hours in vitro. Fluorescence was measured wi th a fluorescence spectrophotometer in cell cultures and in the brain sections. Porphyrins were detected in vitro in the tumour cells from 2 hours onwards and ex vivo in the tumour sections mainly from 2 to 8 h ours, by 22 hours porphyrin fluorescence had almost disappeared. The c ontralateral brain showed low fluorescence levels between 2 and 6 hour s after ALA administration. At the site of the cryo-lesions low fluore scence was measured 6 hours after ALA administration. The 9L tumours f luoresced homogeneously, with a sharp demarcation towards normal brain tissue. Fluorescence in the C6 rumours was patchy, with a poorly fluo rescing edge. In both tumour models fluorescence was also detected in brain surrounding the tumour and sometimes in contralateral white matt er and ventricle ependyma and pia mater. The slight increase of porphy rin fluorescence in the normal brain of tumour bearing rats, compared to the absence of this in rats without a tumour, was attributed to tra nsport by bulk flow of porphyrins made in the tumours, and possibly al so of circulating porphyrins or ALA leaking from the tumour vessels.