EFFICACY AND MECHANISM OF ALUMINUM PHTHALOCYANINE AND ITS SULFONATED DERIVATIVES MEDIATED PHOTODYNAMIC THERAPY ON MURINE TUMORS

The efficacy of photodynamic therapy (PDT) mediated by aluminium phtha locyanine (AlPc) and its mono-and disulphonated derivatives (AlPcS1 an d AlPcS2, respectively) on murine EMT-6 tumour were compared in vivo. AlPc (0.25 mu mol/kg) PDT resulted in no tumour recurrence in all trea ted mice. In contrast, PDT with AlPcS1 (2 mu mol/kg) and AlPcS2 (1 mu mol/kg) only produced tumour cure in 75% and 86% of mice, respectively . Immediately after AlPc-PDT, tumour cells were found to be viable as determined by in vitro clonogenicity, but progressive cell death occur red thereafter. In contrast, AlPcS1 and AlPcS2 PDT produced substantia l cell death (approximately 35% and 70%, respectively, of entire tumou r) immediately after phototherapy, and yet further loss of tumour cell viability continued after PDT. In all cases, few vascular effects wer e observed at 0h post-PDT, as indicated by the retention of Tc-99m-MIB I in the tumour. However, the reduction of blood flow in tumours progr essed with time, such that blood flow in tumours fell to approximately 25% of the control level by 24h after both AlPc and AlPcS1 PDT. With AlPcS2, there was only an approximate 50% fall in tumour blood flow by 24h. These results demonstrate a greater PDT efficiency with AlPc on tumour destruction, which is an indirect mechanism involving damage of tumour vasculature, whereas AlPcS2 has a greater effect on direct tum our cytotoxicity and AlPcS1 exerts both direct and indirect modes of a ction against tumours. (C) 1997 Elsevier Science Ltd.