Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma

Background: Successful tumor eradication with photodynamic therapy (PDT) in vivo depends on the optimal combination of treatment parameters. (Low-dose) PDT may additionally induce antitumoral immune responses. Since the naturally occurring hypericin (Hyp) is a promising photosensitizer for PDT, the aim of the study was to investigate phototoxic and immunologic effects of a low-dose Hyp-PDT on murine tumors in contrast to commonly used Hyp-PDT conditions.

Methods: BALB/c mice bearing CT26 colon carcinoma received hypericin intravenously and were irradiated with red LIGHT 0.5-4h later. Tumor development was recorded. Mice were then re-challenged 60 days after the first tumor cell inoculation to investigate an antitumoral immune response.

Results: Different results of tumor/host responses were obtained, ranging from mice exitus over delayed tumor growth to complete tumor regression according to different treatment protocols. PDT with common doses and a 4h drug-light-interval resulted in a four times delayed tumor growth compared to the control groups. PDT with relatively low doses and a drug-light-interval of 0.5h led to 100% tumor eradication. Re-challenge of these mice with CT26 mouse colon carcinoma cells prevented new tumor growth.

Conclusions: Not only drug concentrations and LIGHT doses seem to determine the efficiency of tumor eradication, but also the localization of hypericin at the time of irradiation. Targets in our low-dose PDT protocol are exclusively the vessels. The advantage of this low-dose PDT beside less drug and LIGHT exposure of the Animals is reduced skin damage, faster healing of the lesions and induction of an antitumoral immune response.