Epidermal growth factor receptor: targeted photoimmunotherapy is fluence rate dependent in-vivo (Conference Presentation)

Photodynamic therapy (PDT) has been used clinically for the treatment of head and neck cancer. The effectiveness of PDT is often strongly dependent on fluence rate. Targeted photo-immunotherapy (PIT) may reduce the adverse effects of non-targeted PDT. The in-vivo distribution of the anti-EGFR targeted conjugate Cetuximab-IRDye700DX was investigated. Vascular and tumor responses were determined with respect to fluence rate. Intra-vital confocal microscopy of skin-fold chambers with the EGFR-overexpressing OSC-19 tumor showed peak tumor fluorescence 24 hrs after administration. Tumor to normal ratio was 3.1±1.6 (n=8). Tumor vascular responses were determined by imaging rhodamine-dextran extravasation. Two hrs after illumination (24 hr DLI, 100 J.cm-2 at 50 mW.cm-2) showed no leakage in 3 of 4 animals and stasis in 1. Normal vasculature showed mild to severe constriction of larger vessels up to 48 hrs after illumination. Subcutaneous OSC-19 tumors were transdermally illuminated with 100 J.cm-2 at 20, 50 and 150 mW.cm-2. Control tumors took 5.3±1.1 days to grow to 200%. All animals treated with 20 mW.cm-2 showed no tumor up to 90 days post treatment (n=4) compared to 1 of 4 in the 50 and 150 mW.cm-2 groups. The remaining tumors reached 200% after 17.9±5.2 and 19.5±7.4 days. Crust formation of the overlying skin was observed at low fluence rate. Cetuximab-IRDye700DX showed significant tumor to normal ratio. Normal tissue responses like vascular effects and crust formation of the skin was observed and may be caused by conjugate still present in the circulation. The effect of targeted-PIT is strongly dependent on fluence rate.