In vivo magnetic resonance measures of dark cytotoxicity of photosensitizers in a murine tumor model

Photodynamic therapy (PDT) is a novel cancer treatment modality where the therapeutic action is controlled by light and the potency of the photosensitizer used. Development of new potent photosensitizers (PS) for clinical applications requires that the PDT effects are maximized while minimizing dark cytotoxicity. The dark toxicity of photosensitizers is generally confirmed using cell lines. Photososensitizers that appear promising from in vitro assays need further investigations under in vivo conditions. As in vivo MR methods have the potential to provide information on the tumor status, they can be very effective tools to study dark toxicity of tumors. The tumor produced on the mouse foot dorsum was tested on two newly synthesized photosensitizers along with Photofrin as a control. The MR studies consisted of serial ³¹P spectral measurements both before and after PS injection. The results show significant changes in the tumor metabolism with increased inorganic phosphate while using new photosensitizers. However these changes slowly approached control levels several hours later. The studies performed while using Photofrin did not show any significant changes indicating minimal or no dark cytotoxicity. Similar studies performed on normal tissue such as the muscle indicated that the energy metabolism was minimally compromised. Our studies demonstrate that the effects of dark cytotoxicity can be observed by ³¹P MR. The growth profiles of tumors treated with PS alone indicate that the metabolic changes are temporary and do not interfere with the tumor growth. The studies suggest that MR is a new method of monitoring the effect of PS administered toxicity in an in vivo model.