Antivascular treatment of solid melanoma tumors with bacteriochlorophyll-serine-based photodynamic therapy

We describe here a strategy for photodynamic eradication of solid melanoma tumors that is based on photoinduced vascular destruction. The suggested pr otocol relies on synchronizing illumination with maximal circulating drug c oncentration in the tumor vasculature attained within the first minute afte r administrating the sensitizer. This differs from conventional photodynami c therapy (PDT) of tumors where illumination coincides with a maximal conce ntration differential of sensitizer in favor of the tumor, relative to the normal surrounding tissue. This time window is often achieved after a delay (3-48 h) following sensitizer administration. We used a novel photosensiti zer, bacteriochlorophyll-serine (Bchl-Ser), which is water soluble, highly toxic upon illumination in the near-infrared (lambda (max) 765-780 nm) and clears from the circulation in less than 24 h, Nude CD1 mice bearing malign ant M2R melanotic melanoma xenografts (76-212 mm(3)) received a single comp lete treatment session. Massive vascular damage was already apparent Ih aft er treatment. Changes in vascular permeability were observed irt vivo using contrast-enhanced magnetic resonance imaging (MRI), with the contrast reag ent Gd-DTPA, by shortening spin-spin relaxation time because of hemorrhage formation and by determination of vascular macromolecular leakage. Twenty-f our hours after treatment a complete arrest of vascular perfusion was obser ved by Gd-DTPA-enhanced MRI, Histopathology performed at the same time conf irmed primary vascular damage with occlusive thrombi, hemorrhage and tumor necrosis, The success rate of cure of over 80% with Bchl-Ser indicates the benefits of the short and effective treatment protocol. Combining the sensi tizer administration and illumination steps into one treatment session (30 min) suggests a clear advantage for future PDT of solid tumors.