dihematoporphyrin ether

Summary

Summary: The purified component of HEMATOPORPHYRIN DERIVATIVE, it consists of a mixture of oligomeric porphyrins. It is used in photodynamic therapy (HEMATOPORPHYRIN PHOTORADIATION); to treat malignant lesions with visible light and experimentally as an antiviral agent. It is the first drug to be approved in the use of PHOTODYNAMIC THERAPY in the United States.

Top Publications

  1. Eljamel M. New light on the brain: The role of photosensitizing agents and laser light in the management of invasive intracranial tumors. Technol Cancer Res Treat. 2003;2:303-9 pubmed
    ..More work needs to be done to refine this promising technology to exploit it to its full potential. ..
  2. Wong T, Tracy E, Oseroff A, Baumann H. Photodynamic therapy mediates immediate loss of cellular responsiveness to cytokines and growth factors. Cancer Res. 2003;63:3812-8 pubmed
    ..This effect of PDT has to be considered when predicting outcome of PDT. ..
  3. Hajri A, Wack S, Meyer C, Smith M, Leberquier C, Kedinger M, et al. In vitro and in vivo efficacy of photofrin and pheophorbide a, a bacteriochlorin, in photodynamic therapy of colonic cancer cells. Photochem Photobiol. 2002;75:140-8 pubmed
    ..The current study suggests a preferential use of Photofrin in PDT of colonic cancer because it should be more effective in vivo than Ph a as a consequence of better tumor uptake. ..
  4. Ferrario A, Luna M, Rucker N, Wong S, Gomer C. Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness. Lasers Surg Med. 2011;43:644-50 pubmed publisher
    ..The polyphenol EGCG improves PDT efficacy by increasing tumor apoptosis and decreasing expression of pro-survival and angiogenic molecules within the tumor microenvironment. ..
  5. Peng Q, Warloe T, Moan J, Godal A, Apricena F, Giercksky K, et al. Antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy can be enhanced by the use of a low dose of photofrin in human tumor xenografts. Cancer Res. 2001;61:5824-32 pubmed
    ..These data indicate that targeting both neoplastic cells and stroma with ALA and Pf (a low dose) can potentiate antitumor PDT effect with no risk of prolonged skin photosensitivity. ..
  6. Luo S, Xing D, Wei Y, Chen Q. Inhibitive effects of photofrin on cellular autophagy. J Cell Physiol. 2010;224:414-22 pubmed publisher
  7. Rigual N, Thankappan K, Cooper M, Sullivan M, Dougherty T, Popat S, et al. Photodynamic therapy for head and neck dysplasia and cancer. Arch Otolaryngol Head Neck Surg. 2009;135:784-8 pubmed publisher
    ..Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. clinicaltrials.gov Identifier: NCT00530088. ..
  8. Chwiłkowska A, Saczko J, Modrzycka T, Marcinkowska A, Malarska A, Bielewicz J, et al. Uptake of photofrin II, a photosensitizer used in photodynamic therapy, by tumour cells in vitro. Acta Biochim Pol. 2003;50:509-13 pubmed
    ..As determined from the total fluorescence intensity, the uptake of PII was only slightly higher for Jurkat than for MCF 7 cells. Nevertheless the kinetics of the uptake was found to be different for both cell lines. ..
  9. Saczko J, Mazurkiewicz M, Chwiłkowska A, Kulbacka J, Kramer G, Ługowski M, et al. Intracellular distribution of Photofrin in malignant and normal endothelial cell lines. Folia Biol (Praha). 2007;53:7-12 pubmed
    ..Our results based on the mitochondrial localization support the idea that PDT can contribute to elimination of malignant cells by inducing apoptosis, which is of physiological significance. ..

More Information

Publications62

  1. Dysart J, Patterson M. Characterization of Photofrin photobleaching for singlet oxygen dose estimation during photodynamic therapy of MLL cells in vitro. Phys Med Biol. 2005;50:2597-616 pubmed
    ..048 +/- 0.005 micros. The generation of fluorescent photoproducts was not a result of singlet oxygen reactions exclusively, and therefore did not yield additional information to aid in quantifying singlet oxygen dose. ..
  2. Korbelik M, Krosl G. Photofrin accumulation in malignant and host cell populations of various tumours. Br J Cancer. 1996;73:506-13 pubmed
    ..The TAM subpopulation that accumulates by far the highest cellular Photofrin levels in tumours is suggested to be responsible for the tumour-localised photosensitiser fluorescence. ..
  3. Saczko J, Kulbacka J, Chwilkowsa A, Pola A, Lugowski M, Marcinkowska A, et al. Cytosolic superoxide dismutase activity after photodynamic therapy, intracellular distribution of Photofrin II and hypericin, and P-glycoprotein localization in human colon adenocarcinoma. Folia Histochem Cytobiol. 2007;45:93-8 pubmed
    ..The weaker accumulation of photosensitizing agents enhances the antioxidant response, and this could influence the efficacy of PDT. ..
  4. Au C, Luk S, Jackson C, Ng H, Yow C, To S. Differential effects of photofrin, 5-aminolevulinic acid and calphostin C on glioma cells. J Photochem Photobiol B. 2006;85:92-101 pubmed
    ..Taken together, PDT could be useful in the treatment of gliomas but the choice of photosensitisers must be taken into consideration. ..
  5. Hsieh Y, Yu J, Lyu P. Characterization of photodynamic therapy responses elicited in A431 cells containing intracellular organelle-localized photofrin. J Cell Biochem. 2010;111:821-33 pubmed publisher
    ..Microtubule dynamics did not significantly affect PV formation. This study demonstrates that cells in which intracellular organelles are selectively loaded with Photofrin mount a novel response to ER stress induced by PDT. ..
  6. Szokalska A, Makowski M, Nowis D, Wilczynski G, Kujawa M, Wojcik C, et al. Proteasome inhibition potentiates antitumor effects of photodynamic therapy in mice through induction of endoplasmic reticulum stress and unfolded protein response. Cancer Res. 2009;69:4235-43 pubmed publisher
    ..The results of these studies are of immediate clinical application because bortezomib is a clinically approved drug that undergoes extensive clinical evaluations for the treatment of solid tumors. ..
  7. Cecic I, Korbelik M. Deposition of complement proteins on cells treated by photodynamic therapy in vitro. J Environ Pathol Toxicol Oncol. 2006;25:189-203 pubmed
    ..The fact that PDT-treated cells are recognized by the complement system as their target adds an important element for understanding the mechanism of tumor response to PDT. ..
  8. Korbelik M, Cecic I. Complement activation cascade and its regulation: relevance for the response of solid tumors to photodynamic therapy. J Photochem Photobiol B. 2008;93:53-9 pubmed publisher
    ..The use of various agents promoting complement activity appears promising for employment as adjuvants to PDT. ..
  9. Usuda J, Tsunoda Y, Ichinose S, Ishizumi T, Ohtani K, Maehara S, et al. Breast cancer resistant protein (BCRP) is a molecular determinant of the outcome of photodynamic therapy (PDT) for centrally located early lung cancer. Lung Cancer. 2010;67:198-204 pubmed publisher
    ..Photofrin may be a substrate of BCRP and be pumped out from the cells, therefore, BCRP may be a molecular determinant of the outcome of Photofrin-PDT...
  10. Yang V, Muller P, Herman P, Wilson B. A multispectral fluorescence imaging system: design and initial clinical tests in intra-operative Photofrin-photodynamic therapy of brain tumors. Lasers Surg Med. 2003;32:224-32 pubmed
    ..The system performed to specification under realistic operating conditions and could reveal unresected residual tumor tissue. It may be used for either PDT dosimetry/monitoring and/or for surgical guidance. ..
  11. Saczko J, Chwiłkowska A, Kulbacka J, Berdowska I, Zielinski B, Drag Zalesinska M, et al. Photooxidative action in cancer and normal cells induced by the use of photofrin in photodynamic therapy. Folia Biol (Praha). 2008;54:24-9 pubmed
    ..Our studies confirm that SOD is involved in the response of both cancer and normal cells to PDT. ..
  12. Biel M. Advances in photodynamic therapy for the treatment of head and neck cancers. Lasers Surg Med. 2006;38:349-55 pubmed
  13. Chang C, Yu J, Wei F. In vitro and in vivo photosensitizing applications of Photofrin in malignant melanoma cells. Chang Gung Med J. 2008;31:260-7 pubmed
    ..Detection of the photosensitizer Photofrin was localized and its distribution fully observed. PDT-Photofrin has the capability to destroy MMCs through in vitro and in vivo SIM treatment. ..
  14. Cuenca R, Allison R, Sibata C, Downie G. Breast cancer with chest wall progression: treatment with photodynamic therapy. Ann Surg Oncol. 2004;11:322-7 pubmed
    ..To date, the response is prolonged and offers good local control. Surgical oncologists have an active role in this treatment option. ..
  15. Makowski M, Grzela T, Niderla J, ŁAzarczyk M, Mróz P, Kopeé M, et al. Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. Clin Cancer Res. 2003;9:5417-22 pubmed
    ..COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination. ..
  16. Jiang F, Robin A, Katakowski M, Tong L, Espiritu M, Singh G, et al. Photodynamic therapy with photofrin in combination with Buthionine Sulfoximine (BSO) of human glioma in the nude rat. Lasers Med Sci. 2003;18:128-33 pubmed
    ..In vivo combination PDT-BSO treatment of U87 tumour rats exhibited significantly more tumour necrosis than individual treatments. In conclusion, our data suggests BSO enhances Photofrin PDT treatment of human glioma. ..
  17. Ferrario A, Rucker N, Wong S, Luna M, Gomer C. Survivin, a member of the inhibitor of apoptosis family, is induced by photodynamic therapy and is a target for improving treatment response. Cancer Res. 2007;67:4989-95 pubmed
  18. Wilson B, Olivo M, Singh G. Subcellular localization of Photofrin and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to photofrin-mediated photodynamic therapy. Photochem Photobiol. 1997;65:166-76 pubmed
    ..Clonogenic survival demonstrated cross-resistance to incubation in PpIX but not to ALA-induced PpIX, implying differences in mitochondrial localization and/or binding, depending on the source of the PpIX within the cells. ..
  19. Eljamel M, Goodman C, Moseley H. ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre Phase III randomised controlled trial. Lasers Med Sci. 2008;23:361-7 pubmed
    ..A multicentre randomized controlled trial is warranted to confirm these results. ..
  20. Woods J, Traynor N, Brancaleon L, Moseley H. The effect of photofrin on DNA strand breaks and base oxidation in HaCaT keratinocytes: a comet assay study. Photochem Photobiol. 2004;79:105-13 pubmed
  21. Hsieh Y, Wu C, Chang C, Yu J. Subcellular localization of Photofrin determines the death phenotype of human epidermoid carcinoma A431 cells triggered by photodynamic therapy: when plasma membranes are the main targets. J Cell Physiol. 2003;194:363-75 pubmed
  22. Schweitzer V. PHOTOFRIN-mediated photodynamic therapy for treatment of early stage oral cavity and laryngeal malignancies. Lasers Surg Med. 2001;29:305-13 pubmed
  23. Zhang X, Jiang F, Kalkanis S, Yang H, Zhang Z, Katakowski M, et al. Combination of surgical resection and photodynamic therapy of 9L gliosarcoma in the nude rat. Photochem Photobiol. 2006;82:1704-11 pubmed
    ..Our results suggest that PDT enhances the efficacy of surgical resection in the management of malignant gliomas without increasing VEGF expression in the BAT. ..
  24. Madan V, Loncaster J, Allan D, Lear J, Sheridan L, Leach C, et al. Nodular basal cell carcinoma in Gorlin's syndrome treated with systemic photodynamic therapy and interstitial optical fiber diffuser laser. J Am Acad Dermatol. 2006;55:S86-9 pubmed
    ..Interstitially placed optical diffuser fibers were used to deliver light. Good response to treatment was seen on clinical evaluation and on measurement by a 20-MHz high-resolution ultrasound...
  25. Fuks D, Bartoli E, Delcenserie R, Yzet T, Celice P, Sabbagh C, et al. Biliary drainage, photodynamic therapy and chemotherapy for unresectable cholangiocarcinoma with jaundice. J Gastroenterol Hepatol. 2009;24:1745-52 pubmed publisher
    ..The combination of photodynamic therapy and biliary stenting seems to be beneficial in the palliative treatment of unresectable cholangiocarcinoma. We aimed to assess the accuracy of photodynamic therapy in a single centre...
  26. Gao S, Wang L, Feng X, Qu Z, Shan T, Xie X. [Absorption and elimination of photofrin-II in human immortalization esophageal epithelial cell line SHEE and its malignant transformation cell line SHEEC]. Ai Zheng. 2009;28:1248-54 pubmed
    ..The photofrin-II contents of SHEE and SHEEC showed a slight change after 15-30 min, and diminished rapidly after 30 min. High photosensitizer concentration in tumor tissues may be not correlated with the affinity of tumor cells. ..
  27. Gill K, Wolfsen H, Preyer N, Scott M, Gross S, Wallace M, et al. Pilot study on light dosimetry variables for photodynamic therapy of Barrett's esophagus with high-grade dysplasia. Clin Cancer Res. 2009;15:1830-6 pubmed publisher
    ..The porfimer sodium content of Barrett's and normal tissue is not significantly different. "Photodynamic dose" for esophageal PDT should incorporate the esophageal thickness. ..
  28. Awan M, Tarin S. Review of photodynamic therapy. Surgeon. 2006;4:231-6 pubmed
    ..However in selective cases of AMD, it has shown success in restoring sight, especially in the 'classic' form of the disease. PDT is also being used to treat a range of solid cancers and non malignant conditions ..
  29. Usui M, Miyagi M, Fukasawa S, Hara T, Ueyama N, Nakajima H, et al. A first trial in the clinical application of photodynamic therapy for the prevention of restenosis after coronary-stent placement. Lasers Surg Med. 2004;34:235-41 pubmed
    ..20%, 0.37+/-0.18 mm, and 0.19+/-0.12, respectively. No in-stent restenosis was observed. This study suggests that PDT, with local delivery of Porfimer sodium, is safe and may be a feasible technique in preventing in-stent restenosis. ..
  30. You Y, Gibson S, Hilf R, Davies S, Oseroff A, Roy I, et al. Water soluble, core-modified porphyrins. 3. Synthesis, photophysical properties, and in vitro studies of photosensitization, uptake, and localization with carboxylic acid-substituted derivatives. J Med Chem. 2003;46:3734-47 pubmed
    ..Inhibition of mitochondrial cytochrome c oxidase activity in whole R3230AC cells was observed in the dark with compounds 1 and 30 and both in the dark and in the light with core-modified porphyrin 2. ..
  31. Lane N. New light on medicine. Sci Am. 2003;288:38-45 pubmed
  32. Moriwaki S, Misawa J, Yoshinari Y, Yamada I, Takigawa M, Tokura Y. Analysis of photosensitivity in Japanese cancer-bearing patients receiving photodynamic therapy with porfimer sodium (Photofrin). Photodermatol Photoimmunol Photomed. 2001;17:241-3 pubmed
    ..These results suggest that the prolonged photosensitivity occurs after PF-PDT especially in female patients and in cases with a lighter SPT. Such patients should be carefully followed up for post-PDT photosensitivity. ..
  33. Krammer B, Hubmer A, Hermann A. Photodynamic effects on the nuclear envelope of human skin fibroblasts. J Photochem Photobiol B. 1993;17:109-14 pubmed
  34. Topazian M, Zhong N, Baron T, Vege S, Wang K. Photodynamic therapy of intraductal papillary mucinous neoplasm. Endoscopy. 2012;44:213-5 pubmed publisher
    ..Metastatic cancer was diagnosed 2 years after PDT had been initiated. Pancreatic PDT was well tolerated in this case, and may be a therapeutic option for selected patients with IPMN of the main pancreatic duct. ..
  35. Xu Z, Li X, Chen S, Cheng Y, Deng J, Wang Z. Glioma stem-like cells are less susceptible than glioma cells to sonodynamic therapy with photofrin. Technol Cancer Res Treat. 2012;11:615-23 pubmed
    ..Thus, cellular differences in sonosensitizer uptake and ROS production influence the antitumor effects of SDT. Furthermore, the resistance of GSCs may be caused by decreased sonosensitizer uptake due to ABCG2 overexpression. ..
  36. Wang L, Huang Z, Lin H, Li Z, Hetzel F, Liu Md B. Effect of Photofrin-mediated photocytotoxicity on a panel of human pancreatic cancer cells. Photodiagnosis Photodyn Ther. 2013;10:244-251 pubmed publisher
    ..BxPc-3, Mia PaCa-2, MPanc-96, and PANC-1 cells were more sensitive and HPAF-II and PL-45 cells less sensitive. Photofrin PDT can induce apoptosis and inhibit survival of human pancreatic cancer cells. ..
  37. Prasad G, Wang K, Buttar N, Wongkeesong L, Lutzke L, Borkenhagen L. Predictors of stricture formation after photodynamic therapy for high-grade dysplasia in Barrett's esophagus. Gastrointest Endosc. 2007;65:60-6 pubmed
    ..The use of centering balloons was not associated with a statistically significant reduction in the risk of stricture formation. ..
  38. Nowak Sliwinska P, Karocki A, Elas M, Pawlak A, Stochel G, Urbanska K. Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells. Biochem Biophys Res Commun. 2006;349:549-55 pubmed
    ..Our results confirm that singlet molecular oxygen based mechanism, prevalent for Verteporfin and PfII, was highly effective against melanoma cells. Verteporfin can be used at small doses with high cellular damage efficiency. ..
  39. Kato H, Usuda J, Okunaka T, Furukawa K, Honda H, Sakaniwa N, et al. Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital. Lasers Surg Med. 2006;38:371-5 pubmed
    ..Moreover, we introduce basic research on cancers and infectious diseases in order to expand the clinical applications of PDT. ..
  40. Yumita N, Han Q, Umemura S. Sonodynamically induced apoptosis with porfimer sodium in HL-60 cells. Anticancer Drugs. 2007;18:1149-56 pubmed
  41. Ortner M. Photodynamic therapy in cholangiocarcinomas. Best Pract Res Clin Gastroenterol. 2004;18:147-54 pubmed
    ..However, before initiating PDT or any other palliative measure, a proper staging and a surgical consultation is necessary to avoid missing a curative surgical option. ..
  42. Gloi A, Beck E. Biodistribution of three photosensitizers in dogs with spontaneous tumors. Vet Ther. 2003;4:155-65 pubmed
    ..As a result, porfimer sodium showed a good selectivity in tumors located in muscle and skin. The study provided clinical information for determination of the efficacy of different PDT alternatives. ..
  43. Gross E, Ehrenberg B. The partition and distribution of porphyrins in liposomal membranes. A spectroscopic study. Biochim Biophys Acta. 1989;983:118-22 pubmed
    ..PF-II was found to reside deeper in the membrane than HPD. Cholesterol was found to modulate the distribution of the two dyes to a greater extent then DPPC and DMPC. The modulation mechanism is discussed. ..
  44. Metz J, Friedberg J. Endobronchial photodynamic therapy for the treatment of lung cancer. Chest Surg Clin N Am. 2001;11:829-39 pubmed
  45. Reuther T, Kübler A, Zillmann U, Flechtenmacher C, Sinn H. Comparison of the in vivo efficiency of photofrin II-, mTHPC-, mTHPC-PEG- and mTHPCnPEG-mediated PDT in a human xenografted head and neck carcinoma. Lasers Surg Med. 2001;29:314-22 pubmed
    ..mTHPC and mTHPCnPEG are promising photosensitizers for the future, especially for the cosmetic treatment needs of head and neck surgery. ..
  46. Gibson S, Van der Meid K, Murant R, Hilf R. Increased efficacy of photodynamic therapy of R3230AC mammary adenocarcinoma by intratumoral injection of Photofrin II. Br J Cancer. 1990;61:553-7 pubmed
    ..The greater delay in tumour growth observed after intratumoral administration of Photofrin II suggests a mechanism favouring direct cell damage. ..
  47. Rogers G. Continuous low-irradiance photodynamic therapy: a new therapeutic paradigm. J Natl Compr Canc Netw. 2012;10 Suppl 2:S14-7 pubmed
    ..The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system. ..
  48. Häberlein H, Both P, Doss M. On the preparation of dihematoporphyrin ether-free hematoporphyrin derivative. Biol Chem Hoppe Seyler. 1988;369:667-70 pubmed
    A dihematoporphyrin ether-free hematoporphyrin derivative has been prepared by a base-catalysed dehydration of hematoporphyrin with sodium hydroxide. The identification was performed by HPLC and mass spectroscopy (FD-MS)...
  49. Zhou Z, Yang H, Xu Y, Zhang Z. Raman spectroscopic study of microcosmic photodamage of the space structure of DNA sensitized by Yangzhou haematoporphyrin derivative and Photofrin II. J Photochem Photobiol B. 1999;52:30-4 pubmed
  50. Goetz C, Hasan A, Stummer W, Heimann A, Kempski O. Experimental research photodynamic effects in perifocal, oedematous brain tissue. Acta Neurochir (Wien). 2002;144:173-9; discussion 179 pubmed
    ..In the clinical setting however, defined damage to peritumoural tissue may be advantageous. This should be achievable by optimised timing and dosage of photodynamic therapy. ..
  51. Manyak M, Ogan K. Photodynamic therapy for refractory superficial bladder cancer: long-term clinical outcomes of single treatment using intravesical diffusion medium. J Endourol. 2003;17:633-9 pubmed
    ..Patients who achieve a CR have less likelihood of and longer time interval before needing cystectomy for progressive disease than NR patients. Our PDT protocol is associated with minimal morbidity in these high-risk patients. ..
  52. Hu X, Feng Y, Lu J, Allison R, Cuenca R, Downie G, et al. Modeling of a type II photofrin-mediated photodynamic therapy process in a heterogeneous tissue phantom. Photochem Photobiol. 2005;81:1460-8 pubmed
    ..We also discuss the utility of this model toward the understanding of clinical PDT treatment of chest wall recurrence of breast carcinoma. ..
  53. Dubreta K, Ivankovic S, Lovrencic Huzjan A, Bosnar Puretic M, Stojkovic R, Jurin M. The characterization of blood flow changes in mouse tumor during Photofrin-based photodynamic therapy by using the color Doppler ultrasonography. Oncol Rep. 2009;22:1253-7 pubmed
    ..Pronounced changes in tumor blood vessel tone might be an additional stress for such vessels leading to their ultimate destruction. ..