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. 2015 Dec 8;16(12):29236-49.
doi: 10.3390/ijms161226162.

Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

Luis B Rocha  1   2 , Fábio Schaberle  3 , Janusz M Dąbrowski  4 , Sérgio Simões  5 , Luis G Arnaut  6
Affiliations

Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

Luis B Rocha et al. Int J Mol Sci. .

Abstract

We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm² led to the complete tumour regression in 83% of the mice.

Keywords: bacteriochlorin; cancer treatment; intravenous formulation; photodynamic therapy; redaporfin; rodents; single-dose toxicity.

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Figures

Figure 1
Figure 1
Summary of the most relevant results from serum biochemistry of Wistar rats, presented as average ± SD. (*** difference relative to the control group—p < 0.001). The two panels present the same results in different scales to highlight the inter-group differences.
Figure 2
Figure 2
Summary of the most relevant results from Wistar rats haematology, presented as average ± SD. The values for the neutrophils (NE) and lymphocytes (LY) populations are presented in the secondary vertical axis. (*** difference relative to the control group—p <0.001; ## difference relative to the 1.5 mg/kg group—p < 0.01).
Figure 3
Figure 3
Kaplan Meier plot for BALB/c animals with CT26 untreated tumours and tumours treated with PDT with total light doses of 74 J/cm2 (130 mW) at 15 min after 1.5 mg/kg of redaporfin administration.
See this image and copyright information in PMC

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