Monitoring PDT effects in murine tumors by spectroscopic and imaging techniques

The changes in the tumor that occur following photodynamic therapy (PDT) were studied using a small animal MR imager operating at 7Tesla. The animal model used in these studies was mice bearing radiation induced fibrosarcoma (RIF) tumor on the foot dorsum. The mice were injected with 10μM/kg of one of the photosensitizers: 1) Photofrin® 2) Non-fluorinated porphyrin photosensitizer (DOD-1) 3) Fluorinated porphyrin photosensitizer (DOD-2) and, 4) Fluorinated chlorin photosensitizer (DOD-6). Laser light at 630 or 650 nm (150 mW/cm², 270 joules/ cm²) was delivered to the tumor at 2-24 hours of photosensitizer administration. The MR spectroscopic and imaging examination of the tumors involved both the ¹H and ³¹P nuclei. The tumor bioenergetics was measured by ³¹P spectroscopy. The water proton relaxivity and diffusion measurements were used to obtain local changes in different regions of the tumor. Changes in ³¹P MR spectra were observed following PDT using Photofrin® and fluorinated chlorin sensitizer (DOD-6). However, no significant changes were observed when the fluorinated porphyrin and its nonfluorinated analog were used. The PDT induced changes in tumor volumes showed significant tumor regression with Photofrin®, fluorinated porphyrin and chlorin sensitizers. No tumor regression was observed with the non labeled porphyrin sensitizer and the growth profile followed the general pattern of unperturbed tumors. Serial noninvasive measurements of tumor response to PDT are measurable by both MRI and MRS. The MR derived parameters that are characteristic of the tumor status before and after the therapy are discussed here.