Figure 1.

Characterizing the radiation-enhanced delivery of macromolecules and nanoparticles. (A) Following 15 Gy “ablative” irradiation of a fluorescent MCF7^GFP-IBD xenograft tumor, the microvasculature visualized through the skin (negative contrast) appears grossly patent through 7 days, before eventually collapsing. (B) At 3 days after 15 Gy irradiation, the macromolecular blood pool agent AngioSense 750 extravasates into MCF7^GFP-IBD xenograft tumor parenchyma (green autofluorescence). (C) IVIS imaging of AngioSense 750 accumulation (black to yellow gradient) in MCF7^GFP-IBD hindlimb tumors demonstrates preferential accumulation and retention after irradiation. Times listed indicate time that has passed following AngioSense administration on day 3 after irradiation. (D) Quantitation of AngioSense 750 IVIS imaging demonstrates increasing accumulation/retention with radiation dose to MCF7^GFP-IBD flank tumors when probe was injected 3 days after irradiation. *p ≤ 0.05 compared to control, n = 5. (E) IVIS imaging of differential distribution (blue to red gradient) of AngioSPARK 680 PEGylated iron oxide nanoparticles after i.v. injection 3 days after 15 Gy irradiation of a MCF7^GFP-IBD flank tumor (dorsal view, upper panel; ventral view, lower panel). Note enhanced accumulation in irradiated tumor (arrow) compared to lungs, spleen, and/or liver (arrowheads). (F) By 3 h after injection, SAIVI PEGylated 100 nm latex particles remained in circulation in unirradiated tumor tissue, as indicated by endothelial staining with tomato lectin (green, upper panel). By contrast, SAIVI particles spread into the parenchyma in the region where the tumor had been irradiated with 5 Gy, 3 days prior (lower panel).