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Summary Background Retinoblastoma is the most common malignant intraocular tumor in children. The current treatment gives a good vital prognostic but there are several drawbacks to the arsenal of “classical antitumoral” therapies. Photodynamic therapy (PDT) could be an exciting non-toxic and non-mutagenic alternative protocol. Method In this paper, we report about the screening of the in vitro photocytotoxicity of hydrophenylporphyrins and chlorins and their glycoconjugated derivatives in a human retinoblastoma cell line (Y79) and for comparison in a colorectal adenocarcinoma cell line (HT29). Results Despite lower photodynamic activity than that observed for hydroxylated photosensitizers, in particular Foscan® glycoconjugated derivatives display phototoxicity (IC50 2.4–0.05 μM ±10%) against Y79 cells with examples of significant intrinsic cytotoxicity. Amongst them the triglucosyl porphyrin 10 is highly photocytotoxic (IC50 0.9 μM ±10%) but is fully devoid of cytotoxicity (IC50 > 15 μM). The photoactivity is highly modulated by the presence of a diethyleneglycol spacer between the chromophore and the glycoside (compounds 14–17, IC50 0.5, 0.6, 0.05 and 0.35 μM ±10%) and by the anomeric configuration of the sugar (compound 15 and 17, IC50 0.6 and 0.05 μM ±10% respectively). One of the main problems for the use of Foscan® is its poor solubility which might be improved by glycoconjugation. Moreover Foscan has been shown to induce necrosis after PDT leading to a possible ulceration of surrounding tissues unsuitable for a conservative treatment. A preferential mitochondrial subcellular localization which has been previously reported for some glycoconjugated photosensitizers could enhance the contribution of apoptosis process. Conclusion Tri-α-O-galactosyl porphyrin 16 is a better candidate than Foscan® for a clinical application of PDT for a conservative therapy of retinoblastoma.

Summary Purpose Retinoblastoma is the most common primary intraocular tumor in children. In industrialized countries, 95% of patients are cured by chemotherapy and conservative treatments. However, these treatments can increase the risk of secondary tumors in patients with a constitutional alteration of the RB1 gene. Photodynamic therapy represents a nonmutagenic therapeutic approach, and may reduce the incidence of secondary tumors. To study the in vivo efficacy of photodynamic therapy, human retinoblastoma xenografts were established in nude mice. Methods Three xenografted cell lines, RB102-FER, RB109-LAK and RB111-MIL, were characterized and used for therapeutic evaluation. Mice were randomly divided into control and treatment groups with 5–8 mice in each group. Treatment groups received irradiation alone, photosensitizer alone or both in 2 of the 3 models and in the third model, photosensitizer plus irradiation was compared to untreated controls. mTHPC was injected intraperitoneally at a dose of 0.6 mg/kg and verteporfin intravenously at a dose of 1 mg/kg. Illuminations were performed 24 h after mTHPC and 1 h after verteporfin injections. Results A transient but significant response to mTHPC was observed for RB102-FER ( p = 0.03) and a significant response to mTHPC for RB111-MIL ( p −4 ) with partial regression maintained for more than 60 days. No significant difference between the different groups was observed for RB109-LAK, except in the verteporfin plus laser group ( p = 0.01). Conclusions The studies confirmed the suitability of the three xenograft models for the evaluation of photodynamic therapy in retinoblastoma. Our findings suggest that PDT may represent an alternative conservative treatment for these tumors.