29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

Fluence and Fluence Rate Dependence of PDT Induced Vascular Permeability

Abstract-
From tumor specific antibodies to gene therapy, the use of macromolecules in the treatment of cancer continues to be an area of active research. When administered intravenously, the ability of these macromolecules to reach their target, tumor cells, is limited by the barrier function of the tumor vasculature. Treatment modalities which can break this vascular barrier will increase the efficacy of macromolecular based therapies. An increase in vascular permeability is one of the many documented vascular effects of PDT. We are currently exploring ways to optimize this modulation of vascular barrier function with a second generation photosensitizer, HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-). The induced permeability is found to be greatest when HPPH is activated in vivo with extremely low fluences and fluence rates. These treatment conditions maximize the permeability of the vasculature while minimizing vascular occlusion. The permeability of the Colon-26 tumor to 200 nm, fluorescent microspheres is slightly dependent on fluence (13-28 J/cm²), while a strong inverse dependence on fluence rate (3.5-28 mW/cm²) is observed. Activation of HPPH with extremely low fluences and fluence rates increases six fold the delivery of stealth liposome encapsulated doxorubicin (SL-DOX) to the Colon-26 tumor. Further, an improvement in tumor response is found when SL-DOX is combined with this permeabilizing PDT treatment scheme relative to either treatment used alone. The utility of this treatment in the delivery of antibodies, polymer microspheres, and immune effector cells to the tumor will be addressed.

Keywords: vascular permeability, photodynamic therapy, drug delivery, fluence rate