Abstract 3213: Evaluation of porphyrin biodistribution for use in photodynamic therapy of retinoblastoma in transgenic mice

Abstract

Abstract Background: Porphyrins are a group of heterocyclic macrocycle organic compounds. They have shown good efficiency in the photodynamic treatment of tumors in the last twenty years. The photodynamic therapy could be an alternative treatment for retinoblastoma using a photosensitizer with low dark toxicity and low mutagenic properties unlike the conventional chemotherapies. The objectives of this study were to develop a photosensitizer in our lab which is a diethylene glycol mannoconjugated tetraphenyl porphyrin (TPP, MW: 1413.6) and to determine the optimal interval time for photodynamic therapy using the concentration of TPP in eye and blood samples of mice. Materials and method: Transgenic mice developed bilateral retinoblastoma from the retina since 4 weeks of age to 16 weeks of age (tumors fill the ocular globe and the mice will be sacrificed for ethic purpose). The evaluation of the biodistribution of our TPP was realized to know the best drug-light interval to perform the photodynamic therapy. For this purpose, an intraperitoneal injection of 200 µl at 5.25 mg/ml in PEG 400/physiological serum (1:1, v/v) was performed on the LHbetaTag transgenic mice. At different time intervals (8h, 24h, 40h, 48h, and 72h) following injection, the mice were sacrificed and the eyes and blood were collected. TPP in eye samples were extracted in methanol and the level of TPP was measured by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) analysis (0.5-100 ng/mL). The level of TTP in blood samples was quantified after protein precipitation by UPLC-MS/MS method (5.00-1000 ng/mL). Results: We observed a time dependency accumulation of TPP in eyes with observed Tmax=48 hours. TPP serum concentrations decreased by the same manner up to 48 h. The determination of drug-light interval allowed us to perform the light delivery when the TPP level is highest (48 h) in the ocular tumor tissue (retinoblastoma). Conclusions: Our TPP had a good in vitro photocytotoxicity at very low doses and showed a good efficacy in vivo with subcutaneous patient derived retinoblastoma xenografts in immunodeficient mice. The knowledge of Tmax and this interval is essential to realize the photodynamic therapy with the better efficiency, the final goal being to eradicate the retinoblastoma from the retina. Citation Format: Florent Poyer, Samuel Hugeut, Stéphanie Lemaitre, Olivier Madar, Carole D Thomas, Philippe Maillard, Marie-Paule Teulade-Fichou, Nathalie Cassoux, François Doz, Keyvan Rezai. Evaluation of porphyrin biodistribution for use in photodynamic therapy of retinoblastoma in transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3213.