Photofrin Uptake by Murine Macrophages1

The uptake of Photofrin by murine peritoneal macrophages in vivo and in vitro was examined. Cellular Photofrin content was measured either by performing a fluorometric assay or by using )4C-labeled drug. For comparison, the uptake of Photofrin by murine SCCVII tumor cells (squamous cell carcinoma) was also examined under the same conditions. The data demonstrate that macrophages have a much greater capacity for Photofrin uptake than SCCVII tumor cells. Photofrin contents at 24 h after drug administration (25 mg/kg) measured 420 ±90 (SD), 74 ± 15, and 15 ±2 ng//tg of cell protein for peritoneal macrophages, tumorassociated macrophages, and SCCVII tumor cells, respectively. Factors that modify macrophage activity also influence the uptake of the drug by macrophages. The results support the assumption that Photofrin uptake by macrophages is dominated by phagocytosis of highly aggregated components of the drug. In vivo accumulated Photofrin material in peritoneal macrophages, tumor-associated macrophages, and tumor cells has shown very similar in vitro clearance from all three cell types. Only 20-30% of Photofrin was lost from the cells during the initial 24 h, mainly between 1 and 4 h of clearance incubation.