Substance P enhances photosensitizer uptake in MAT-LyLu prostate tumors.

Proc Amer Assoc Cancer Res, Volume 47, 2006 5185 The aim of this study is to characterize the transvascular transport of photosensitizer conjugates in MAT-LyLu subcutaneous tumors and to investigate the effects of inflammatory mediator on the photosensitizer uptake. We have examined the tumor vasculature morphology, pore cutoff size, vascular permeability, and photosensitizer uptake temporal and spatial dynamics and in response to intratumor injection of a neuropeptide, substance P. Average diameter of tumor vessels were increased significantly in response to SP administration. Vessel wall pore cutoff size evaluated by intravital fluorescence microscopy showed SP increased vessel pore cutoff size. This result has been confirmed with electron microscopy illustrated the opening intercellular gaps after injection of SP. Vascular permeability to LDL (22 nm in diameter), BSA (6 nm in diameter), fluorescence dextrans (3, 10, 70, 500, 2,000KDa) and fluorescence beads (40, 200, 1,000 nm in diameter) were determined by intravital fluorescence microscopy. Permeability was found temporally and spatially heterogeneous. Vascular permeability to LDL and BSA were found increased significantly and more homogeneous after SP administration. These changes were further confirmed by Evans Blue albumin extravasation assay showing significant increase of albumin extravasation in SP injected tumors. Photosensitizer uptake was evaluated by fluorescence microscopy and fluorometer at 3 hours post photosensitizer administration. SP injected tumors showed a significant higher cellular uptake and a more homogeneous distribution than the control tumors. Our study suggested that intratumor administration of substance P can induce transient opening of intercellular gaps, enhance the photosensitizer extravasation and achieve a homogeneous photosensitizer cellular uptake.