Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer

Currently delivered light dose (J/cm 2 ) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm 2 ) and associated heating on tumour response and cure. Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin ® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. Light-induced tissue heating in mice was studied with real-time magnetic resonance thermometry. In the mouse model, cure rates of 70–90% were obtained with I-PDT using 8.4–245 mW/cm 2 and ≥45 J/cm 2 in 100% of the SCCVII tumour. Increasing irradiance was associated with increase in tissue heating. I-PDT with Photofrin ® resulted in significantly ( p < 0.05) higher cure rate compared to light delivery alone at same irradiance and light dose. Local control and/or cures of VX2 were obtained using I-PDT with 16.5–398 mW/cm 2 and ≥45 J/cm 2 in 100% of the tumour. In Photofrin ® -mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours.