Comparison of the In Vivo Photodynamic Threshold Dose for Photofrin, Mono‐ and Tetrasulfonated Aluminum Phthalocyanine Using a Rat Liver Model
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abstract
ABSTRACTThe photodynamic threshold dose in normal rat liver was determined from the measured depth of necrosis following surface irradiation. The threshold was determined for the photosensitizing drugs Photofrin and monosulfo‐nated aluminum chlorophthalocyanine, AIPcS1, at 24 h postinjection and was found to be (3.4 ×/÷ 1.3) × 1018 (8.2 ×/÷ 1.5) × 1018photons cm‐3, respectively, compared with the previously reported value of (38 ± 2) × 1018photons cm‐3for the tri/tetrasulfonated phthalocyanine, AlPcS4. These values were independent of drug concentration or total light fluence. For all three drugs the depth of tissue necrosis decreased as the time between drug and light administration increased from 10 min to 72 h. This decrease can be attributed both to the change in the tissue drug concentration as well as to changes in the efficiency of photodynamic therapy for producing tissue damage, related to the photodynamic necrosis threshold. 1'he threshold values for all three photosensitizers were lowest at 10 min post injection: (1.4 ×/÷ 1.4) × 1018, (1.6 ×/÷ 1.3) × 1018 (23 ×/÷ 1.3) × 1018photons cm‐3for Photofrin, AIPcS1 and AlPcS4, respectively. The changes in necrosis threshold with time may be due to an initial change from entirely vascular to a combination of vascular and cellular damage, with later redistribution of the photosensiti/.er to targets at the subcellular level.
