INTERACTION OF THE BIOREDUCTIVE DRUG SR 4233 AND PHOTODYNAMIC THERAPYUSING PHOTOFRIN IN A MOUSE-TUMOR MODEL

Purpose: Combining the bioreductive drug SR 4233 with interstitial pho todynamic therapy to improve efficacy. Methods and Materials: RIF1 tum ors were implanted subcutaneously in mice and treated with interstitia l photodynamic therapy. The bioreductive drug SR 4233 (a benzotriazine which exhibits preferential cell killing under hypoxic conditions) wa s combined with photodynamic therapy to exploit the induced hypoxia. S R 4233 was given to mice prior to or just after illumination. The effe ct of multiple SR 4233 injections given over the first 3 days after tr eatment was also evaluated. Results: The results from experiments with a 24 hr interval between Photofrin and illumination showed that SR 42 33 produced only a small additional growth delay compared with photody namic therapy alone (light doses of 300 or 400 J/cm, combined with 6 x 15 mg/kg SR 4233). Some cures (6/60), however, were found in groups t reated with 200 to 400 J/cm with SR 4233, whereas only two cures (2/77 ) occurred at light doses up to 400 J/cm after photodynamic therapy al one. Reducing the interval between Photofrin injection and illuminatio n increased the number of cures in the combination group, although thi s was associated with a marked increase in toxicity. A small increase in cure rate was observed for the combination of photodynamic therapy (6 hr interval) and SR 4233, although this was not significant due to the limited number of mice that survived treatment. Conclusion: Only a limited effect of combining SR 4233 and interstitial photodynamic the rapy was observed in this tumor model. A possible explanation could be the rapid conversion of SR 4233 into inactive metabolites.