INTERSTITIAL PHOTODYNAMIC THERAPY WITH THE 2ND-GENERATION PHOTOSENSITIZER BACTERIOCHLORIN A IN A RAT MODEL FOR LIVER METASTASES

Bacteriochlorin a (BCA) is a second-generation photosensitizer that is effective in tumour destruction upon illumination with light of a wav elength of 760 nm. Tissue penetration by light at this wavelength is g reater compared with wavelengths at which commonly used photosensitize rs are illuminated, making it possible to treat larger tumours. In a m odel of experimental liver metastases in rats, we measured lesion size s after interstitial illumination of tumours at different times after intravenous administration of BCA (10 mg kg(-1) bodyweight), as well a s BCA concentrations in liver and tumour tissue. In both, BCA concentr ations showed a rapid decline within the first 4 h, followed by a slow decrease over the next 20 h, suggesting biphasic pharmacokinetics. No selective uptake in tumour tissue was observed. A near-linear relatio nship was found between lesion sizes and liver and tumour BCA concentr ations, suggesting that optimal results with photodynamic therapy (PDT ) could be obtained by illumination within a short time interval after administration, when tissue concentrations are highest. No severe liv er toxicity was observed as indicated by serum ALAT levels. However, i n all tumours evaluated, islands of vital-looking cells were present l eading to tumour regrowth within 35 days. In view of the obtained lesi on diameters of approximately 13 mm after BCA-PDT and the rapid cleara nce rate of BCA, the concept of a near-infrared absorbing photosensiti zer for PDT of liver tumours is a potential interesting strategy.