Hypericin is a promising alternative photosensitizer for PDT. Like 5-ALA, it can pass the disturbed bloodbrain barrier and additionally exhibits a high triplet quantum yield that allows for an effective ROS formation . A direct comparison between hypericin and 5-ALA revealed a significantly higher photo-cytotoxicity of hypericin . Hypericin was shown to accumulate in the perinuclear region in various tumor cell lines with main enrichment sites in the endoplasmic reticulum (ER), the Golgi apparatus, mitochondria and lysosomes . This accumulation behavior has a major influence on PDT progression and might affect the actual cell death mechanism. Hypericin uptake and distribution was further studied in tumor spheroid models followed by hypericin PDT .