We describe here a strategy for photodynamic eradication of solid
melanoma tumors that is based on photo-induced vascular destruction. The suggested protocol relies on synchronizing illumination with maximal circulating
drug concentration in the
tumor vasculature attained within the first minute after administrating the sensitizer. This differs from conventional
photodynamic therapy (
PDT) of
tumors where illumination coincides with a maximal concentration 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
photosensitizer,
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 malignant M2R melanotic
melanoma xenografts (76-212 mm3) received a single complete treatment session. Massive vascular damage was already apparent 1 h
after treatment. Changes in vascular permeability were observed in vivo using contrast-enhanced magnetic resonance imaging (MRI), with the contrast
reagent Gd-DTPA, by shortening spin-spin relaxation time because of
hemorrhage formation and by determination of vascular macromolecular leakage. Twenty-four hours
after treatment a complete arrest of vascular perfusion was observed by
Gd-DTPA-enhanced MRI. Histopathology performed at the same time confirmed 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 sensitizer administration and illumination steps into one treatment session (30 min) suggests a clear advantage for future
PDT of solid
tumors.