THE SENSITIVITY OF NORMAL BRAIN AND INTRACRANIALLY IMPLANTED VX2 TUMOR TO INTERSTITIAL PHOTODYNAMIC THERAPY

The applicability and limitations of a photodynamic threshold model, u sed to describe quantitatively the in vivo response of tissues to phot odynamic therapy, are currently being investigated in a variety of nor mal and malignant tumour tissues. The model states that tissue necrosi s occurs when the number of photons absorbed by the photosensitiser pe r unit tissue volume exceeds a threshold. New Zealand White rabbits ev ert sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 rumours were illuminated via an optical f ibre placed into the tissue at craniotomy. The light fluence distribut ion in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determi ned post mortem by absorption spectroscopy. The derived photodynamic t hreshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident b eyond the zone of frank necrosis. For Photofrin the threshold decrease s with time delay between photosensitiser administration and light tre atment. No significant difference in threshold is found between Photof rin and haematoporphyrin derivative. The threshold in normal brain (gr ey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid . The results confirm the very high sensitivity of normal brain to por phyrin photodynamic therapy and show the importance of in situ light f luence monitoring during photodynamic irradiation.