Photodynamic therapy (PDT) for brain tumors appears to be complementary to conventional treatments (Cancer Treat Rev, 2012). Xenografts of human glioblastoma cells were implanted stereotactically in nude rat brain for interstitial PDT (iPDT) of brain tumors guided by real-time imaging. Multifunctional nanoparticles consist of a surface-localized tumor vasculature targeting neuropilin-1 ligand, encapsulated PDT and imaging agents (Nanomedicine, 2011; PLOSOne, 2012). The selected nanoparticles are favourable to a photosensitizer targeting strategy for iPDT combined with MRI (magnetic resonance imaging) (Theranostics, 2012). The experimental values of µa and µs of the tumor tissue were introduced into a model of light propagation for animals with intracranial tumors treated by iPDT. This model of light distribution demonstrates that the absorption and diffusion coefficients influence strikingly photons propagation into the tumor volume and moreover we highlight the importance of the diffuser localization for therapy efficiency, especially to treat tumor thickness greater than 2mm. After intravenous injection of the multifunctional nanoparticles into rats with intracranial glioblastoma, we demonstrated a positive contrast enhancement of the tumor tissue by MRI, allowing the optimization of the optical fiber implantation. iPDT response was assessed by MR imaging, perfusion and diffusion weighted MRI, and MRS, illustrating the influence of the fiber positioning for a good light propagation into the tumor volume. Days of progression free survival were related to a hypoperfusion of the tumor tissue, an increase of apparent coefficient diffusion, and a modification in metabolite profile such as the increase of lactate.