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Porfimer Sodium Versus PS785 for Photodynamic Therapy (PDT) of Lung Cancer Xenografts in Mice

Published:March 10, 2021DOI:https://doi.org/10.1016/j.jss.2020.12.067

      Abstract

      Background

      Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration–approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice.

      Methods

      Human non–small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT.

      Results

      Porfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point.

      Conclusions

      PS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.
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      References

      1. US mortality volumes 1930 to 1959 and US mortality data 1960 to 2014, National Center for Health Statistics, Centers for Disease Control and Prevention.pdf. Available at: https://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_03.pdf. Accessed July 24, 2020.

        • Key Statistics for Lung Cancer
        American Cancer Society.
        (Available at:)
        • Non-Small Cell Lung Cancer Survival Rates, by Stage
        American Cancer Society, American Cancer Society.
        (Available at:)
        • Darling G.E.
        • Allen M.S.
        • Decker P.A.
        • et al.
        Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial.
        J Thorac Cardiovasc Surg. 2011; 141: 662-670
        • Rusch V.W.
        • Hawes D.
        • Decker P.A.
        • et al.
        Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer: report of the ACOSOG Z0040 trial.
        J Clin Oncol. 2011; 29: 4313-4319
        • Moghissi K.
        • Dixon K.
        Is bronchoscopic photodynamic therapy a therapeutic option in lung cancer?.
        Eur Respir J. 2003; 22: 535-541
        • Loewen G.M.
        • Pandey R.
        • Bellnier D.
        • Henderson B.
        • Dougherty T.
        Endobronchial photodynamic therapy for lung cancer.
        Lasers Surg Med. 2006; 38: 364-370
        • Gao Y.H.
        • Zhu X.X.
        • Zhu W.
        • et al.
        Synthesis and evaluation of novel chlorophyll a derivatives as potent photosensitizers for photodynamic therapy.
        Eur J Med Chem. 2020; 187: 111959
        • Calixto G.M.F.
        • de Annunzio S.R.
        • Victorelli F.D.
        • et al.
        Chitosan-based drug delivery systems for optimization of photodynamic therapy: a review.
        AAPS PharmSciTech. 2019; 20: 253
        • Dougherty T.J.
        • Cooper M.T.
        • Mang T.S.
        Cutaneous phototoxic occurrences in patients receiving Photofrin.
        Lasers Surg Med. 1990; 10: 485-488
        • Ash C.
        • Dubec M.
        • Donne K.
        • Bashford T.
        Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods.
        Lasers Med Sci. 2017; 32: 1909-1918
        • Hudson D.E.
        • Hudson D.O.
        • Wininger J.M.
        • Richardson B.D.
        Penetration of laser light at 808 and 980 nm in bovine tissue samples.
        Photomed Laser Surg. 2013; 31: 163-168
        • Tomayko M.M.
        • Reynolds C.P.
        Determination of subcutaneous tumor size in athymic (nude) mice.
        Cancer Chemother Pharmacol. 1989; 24: 148-154
        • Jensen M.M.
        • Jørgensen J.T.
        • Binderup T.
        • Kjaer A.
        Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper.
        BMC Med Imaging. 2008; 8: 16
        • Ikeda N.
        • Usuda J.
        • Maehara S.
        Photodynamic therapy for central-type early-stage lung cancer.
        Gen Thorac Cardiovasc Surg. 2020; 68: 679-683
        • Quirk B.J.
        • Brandal G.
        • Donlon S.
        • et al.
        Photodynamic therapy (PDT) for malignant brain tumors–where do we stand?.
        Photodiagnosis Photodyn Ther. 2015; 12: 530-544
        • Dougherty T.J.
        Photodynamic therapy (PDT) of malignant tumors.
        Crit Rev Oncol Hematol. 1984; 2: 83-116
      2. AAPM Report No. 88. Photodynamic Therapy Dosimetry. Published for the American Association of Physics in Medicine by Medical Physics Publishing, 2005.pdf. Available at: https://www.aapm.org/pubs/reports/rpt_88.pdf. Accessed July 24, 2020.

        • Mitra S.
        • Foster T.H.
        Carbogen breathing significantly enhances the penetration of red light in murine tumours in vivo.
        Phys Med Biol. 2004; 49: 1891-1904
        • Corti L.
        • Toniolo L.
        • Boso C.
        • et al.
        Long-term survival of patients treated with photodynamic therapy for carcinoma in situ and early non-small-cell lung carcinoma.
        Lasers Surg Med. 2007; 39: 394-402
        • Orenstein A.
        • Kostenich G.
        • Roitman L.
        • et al.
        A comparative study of tissue distribution and photodynamic therapy selectivity of chlorin e6, Photofrin II and ALA-induced protoporphyrin IX in a colon carcinoma model.
        Br J Cancer. 1996; 73: 937-944
        • Benayoun L.
        • Schaffer M.
        • Bril R.
        • et al.
        Porfimer-sodium (Photofrin-II) in combination with ionizing radiation inhibits tumor-initiating cell proliferation and improves glioblastoma treatment efficacy.
        Cancer Biol Ther. 2013; 14: 64-74