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Effect of drug–light interval on the mode of action of Photofrin photodynamic therapy in a mouse tumor model

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Abstract

Our objective was to examine the effect of time intervals between Photofrin injection and laser irradiation [i.e., drug–light interval (DLI)] on the mode of action of Photofrin photodynamic therapy (PDT). Kunming mice transplanted with sarcoma-180 cells were used as an animal model. The tumor-bearing mice in the control group were given neither photosensitizer nor laser irradiation. PDT groups were given intravenous (i.v.) injection of Photofrin (7.5 mg/kg) prior to being irradiated with a 630 nm laser at 120 J/cm2 at different DLIs (1 min–48 h). Tumors and overlying skin were visually examined daily. Histopathological and electron microscopic examinations were carried out 48 h after PDT. Survival rates were recorded. The mice in the groups that had experienced short DLIs (<60 min) showed stronger skin reactions than the groups subjected to long DLIs (>6 h). Histological examination showed that antitumor effects were achieved mainly by the destruction of tumor blood vessels and the formation of thrombosis at short DLIs, whereas, at long DLIs, the tumor cells were killed directly by PDT-mediated cytotoxicity. Electron microscopy revealed various degrees of mitochondrial swelling. The survival rate of the mice subjected to long DLIs was slightly higher than that of the mice subjected to short DLIs. Both vascular (e.g., tumor vessel destruction) and cellular (e.g., cytotoxicity) effects contributed to Photofrin PDT-induced tumor ablation.

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References

  1. Dougherty TJ, Kaufman JE, Goldfarb A (1978) Photoradiation therapy for the treatment of malignant tumors. Cancer Res 38:2628–2635

    PubMed  CAS  Google Scholar 

  2. Rosenthal DI, Glatstein E (1994) Clinical applications of photodynamic therapy. Ann Med 26:405–409. doi:10.3109/07853899409148361

    Article  PubMed  CAS  Google Scholar 

  3. Qiang YG, Zhang XP, Li J, Huang Z (2006) Photodynamic therapy for malignant and non-malignant diseases: clinical investigation and application. Chin Med J 119:845–857

    PubMed  CAS  Google Scholar 

  4. Zhou CN (1989) New trends in photobiology: mechanisms of tumor necrosis induced by photodynamic therapy. J Photochem Photobiol B Biol 3:299–318. doi:10.1016/1011–1344(89)80035–1

    Article  CAS  Google Scholar 

  5. Moan J (1990) Properties for optimal PDT sensitizers. J Photochem Photobiol B 5:521–524. doi:10.1016/1011–1344(90)85064–4

    Article  PubMed  CAS  Google Scholar 

  6. Ochsner M (1997) Photophysical and photobiological processes in the photodynamic therapy of tumor. J Photochem Photobiol B 39:1–18. doi:10.1016/S1011–1344(96)07428–3

    Article  PubMed  CAS  Google Scholar 

  7. Henderson BW, Dougherty J (1992) How does photodynamic therapy work. Photochem Photobiol 55:145–157. doi:10.1111/j.1751–1097.1992.tb04222.x

    Article  PubMed  CAS  Google Scholar 

  8. Li LB, Luo RC, Liao WJ, Zhang MJ, Zhou J, Miao JX (2006) Clinical study of Photofrin photodynamic therapy for the treatment of relapse nasopharyngeal carcinoma. Photodiagn Photodyn Ther 3:266–271. doi:10.1016/j.pdpdt.2006.09.004

    Article  CAS  Google Scholar 

  9. Huang Z, Xu H, Meyers AD, Musani AI, Wang L, Tagg R, Barqawi AB, Chen YK (2008) Photodynamic therapy for treatment of solid tumors—potential and technical challenges. Technol Cancer Res Treat 7:309–320

    PubMed  CAS  Google Scholar 

  10. Chen B, Pogue BW, Hoopes PJ, Hasan T (2006) Vascular and cellular targeting for photodynamic therapy. Crit Rev Eukaryot Gene Expr 16:279–305

    PubMed  Google Scholar 

  11. Michels S, Hansmann F, Geitzenauer W (2006) Influence of treatment parameters on selectivity of verteporfin therapy. Invest Ophthalmol Vis Sci 47:371–376. doi:10.1167/iovs05–0354

    Article  PubMed  Google Scholar 

  12. Yuan KH, Li Q, Yu W, Zhang C, Huang Z (2008) Retrospective analysis of treatment of port wine stain birthmarks—photodynamic therapy vs pulsed dye laser. Photodiagn Photodyn Ther 5:50–57. doi:10.1016/j.pdpdt.2007.12.001

    Article  Google Scholar 

  13. Huang Z, Chen Q, Luck D, Beckers J, Wilson BC, Trncic N, Larue SM, Blanc D, Hetzel FW (2005) Studies of a vascular-acting photosensitizer Pd-bacteriopheophorbide (Tookad) in normal canine prostate and spontaneous canine prostate cancer. Lasers Surg Med 36:390–397. doi:10.1002/lsm.20177

    Article  PubMed  CAS  Google Scholar 

  14. Henderson BW, Waldow SM, Mang TS, Potter WR, Malone PB, Dougherty TJ (1985) Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res 45:572–576

    PubMed  CAS  Google Scholar 

  15. Moan J, Berg K (1992) Photochemotherapy of cancer: experimental research. Photochem Photobiol 55:931–948. doi:10.1111/j.1751–1097.1992.tb08541.x

    Article  PubMed  CAS  Google Scholar 

  16. Dougherty TJ, Gomer CJ, Henderson BW (1998) Photodynamic therapy. J Natl Cancer Inst (Bethesda) 90:889–905

    Google Scholar 

  17. Ferrario A, von Tiehl KF, Rucker N (2000) Anti-angiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma. Cancer Res 60:4066–4069

    PubMed  CAS  Google Scholar 

  18. Bellnier DA, Potter WR, Vaughan L (1995) The validation of a new vascular damage assay for photodynamic therapy agents. Photochem Photobiol 62:896–905

    Article  PubMed  CAS  Google Scholar 

  19. Henderson BW, Busch TM, Vaughan LA (2000) Photofrin photodynamic therapy can significantly deplete or preserve oxygenation in human basal cell carcinomas during treatment, depending on fluence rate. Cancer Res 60:525–529

    PubMed  CAS  Google Scholar 

  20. Engbrecht BW, Menon C, Kachur AV, Hahn SM, Fraker DL (1999) Photofrin-mediated photodynamic therapy induces vascular occlusion and apoptosis in a human sarcoma xenograft model. Cancer Res 59:4334–4342

    PubMed  CAS  Google Scholar 

  21. Agarwal ML, Clay ME, Harvey EJ, Evans HH, Antunez AR, Oleinick NL (1991) Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells. Cancer Res 51:5993–5996

    PubMed  CAS  Google Scholar 

  22. He XY, Sikes RA, Thomsen S, Chung LW, Jacques SL (1994) Photodynamic therapy with Photofrin II induces programmed cell death in carcinoma cell lines. Photochem Photobiol 59:468–473. doi:10.1111/j.1751–1097.1994.tb05066.x

    Article  PubMed  CAS  Google Scholar 

  23. Oleinick NL, Evans HH (1998) The photobiology of photodynamic therapy: cellular targets and mechanisms. Radiat Res 150 (Suppl) :S146–S156. doi:10.2307/3579816

    Article  PubMed  CAS  Google Scholar 

  24. Lu ZD, Bian M, Zhang XJ (1983) Electron microscope observation of HPD-laser PDT to S180 cells action. J Chin Med 63:336–338

    CAS  Google Scholar 

  25. Fenning MC, Brown DQ, Chapman JD (1994) Photodosimetry of interstitial light delivery to solid tumors. Med Phys 21:1149–1156. doi:10.1118/1.597342

    Article  PubMed  CAS  Google Scholar 

  26. Johansen LS (1999) Photodynamic therapy. A new method for the treatment of cancer. Ugeskr Laeger 161:3992–3995

    PubMed  CAS  Google Scholar 

  27. Dole KC, Chen Q, Hetzel FW, Whalen LR, Blanc D, Huang Z (2005) Effects of photodynamic therapy on peripheral nerve: in situ compound-action potentials study in a canine model. Photomed Laser Surg 23:172–176. doi:10.1089/pho.2005.23.172

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The authors would like to thank Professor Chuannong Zhou (The Chinese Academy of Medical Sciences) for his insightful discussion.

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Correspondence to Li-Bo Li.

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Li, LB., Luo, RC. Effect of drug–light interval on the mode of action of Photofrin photodynamic therapy in a mouse tumor model. Lasers Med Sci 24, 597–603 (2009). https://doi.org/10.1007/s10103-008-0620-9

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  • DOI: https://doi.org/10.1007/s10103-008-0620-9

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