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

BACKGROUND: 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. METHODS: Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin (R) 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. RESULTS: 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 (R) 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 >= 45J/cm(2) in 100% of the tumour. CONCLUSION: In Photofrin (R)-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.