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Die photodynamische Therapie des Harnblasenkarzinoms

Eine neue Option

Photodynamic therapy of bladder cancer

A new option

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Zusammenfassung

Hintergrund

Das Harnblasenkarzinom ist der dritthäufigste Tumor in Deutschland. Die Resektionstherapie beim oberflächlichen Harnblasenkarzinom (Ta, CIS) sieht derzeit schon die photodynamische Diagnostik (PDD) mit HEXVIX® zur besseren Beurteilung der Tumorausbreitung vor. Versuche, diese Photosensibilisatoren auch zur photodynamischen Therapie (PDT) zu nutzen, haben nur begrenzte Erfolge gezeigt. Insbesondere die zu geringe Gewebepenetration aufgrund der Anregung mit kurzwelligem Licht ist eine wesentliche Einschränkung.

Methode

Im Rahmen eines DFG-Projekts untersuchen wir die Möglichkeiten der PDT mit dem neuen, im nahen Infrarot effektiv anregbarem Photosensibilisator Tetrahydroporphyrin-Tetratosylat (THPTS).

Ergebnisse

Aufgrund des im sog. „phototherapeutischen Fenster“ liegenden Absorptionsmaximums bei 760 nm und der damit möglichen Gewebepenetration von 15 mm ist THPTS auch für die PDT von größeren, soliden Tumoren geeignet, was wir in verschiedenen anderen Tumorentitäten bereits zeigen konnten. Damit könnte die PDT erstmals auch für muskelinvasiv wachsende Harnblasenkarzinome (≥ T2) in Frage kommen. Dies soll in einem orthotopen Rattenharnblasentumormodell überprüft werden.

Abstract

Background

Bladder cancer (BCa) is the third most common tumor in Germany. Currently, resection therapy for superficial BCa (Ta, CIS) includes photodynamic diagnostics (PDD) using HEXVIX® for improved assessment of tumor spread. Trials using these photosensitizers for photodynamic therapy (PDT) showed only limited success. Especially low tissue penetration due to short-wave excitation was a limiting factor.

Methods

This study which was funded by the German Research Foundation (DFG) examined the feasibility of the novel photosensitizer tetrahydroporphyrin-tetratosylate (THPTS) for PDT in a rat bladder cancer model.

Results

As THPTS is very effectively excitable at a near infrared wavelength of 760 nm it is within the so-called phototherapeutic window and allows tissue penetration of up to 15 mm. Thus THPTS can also be used for PDT of larger, solid tumors as was previously demonstrated for other tumor entities. Therefore, effective treatment of even muscle-invasive bladder cancer (≥T2) may become an option using THPTS. In this current study the effectiveness and safety of THPTS-PDT was examined in an orthotopic bladder cancer rat model.

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Literatur

  1. Asanuma H, Arai T, Morimoto Y et al (2005) Photodynamic therapy with PAD-S31, a new hydrophilic chlorin photosensitizer, in an orthotopic rat bladder tumor model. J Urol 174:2016–2021

    Article  PubMed  CAS  Google Scholar 

  2. Babjuk M, Oosterlinck W, Sylvester R et al (2012) Guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). EAU Guidelines 1–35

  3. Braathen LR, Szeimies RM, Basset-Seguin N et al (2007) Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol 56:125–143

    Article  PubMed  Google Scholar 

  4. Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 6:535–545

    Article  PubMed  CAS  Google Scholar 

  5. El Khatib S, Berrahmoune S, Leroux A et al (2006) A novel orthotopic bladder tumor model with predictable localization of a solitary tumor. Cancer Biol Ther 5:1327–1331

    Article  Google Scholar 

  6. Epstein JI, Amin MB, Reuter VR, Mostofi FK (1998) The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 22:1435–1448

    Article  PubMed  CAS  Google Scholar 

  7. Goeckenjan G, Sitter H, Thomas M et al (2011) Prevention, diagnosis, therapy, and follow-up of lung cancer: interdisciplinary guideline of the German Respiratory Society and the German Cancer Society. Pneumologie 65:39–59

    Article  PubMed  CAS  Google Scholar 

  8. Gomer CJ, Ryter SW, Ferrario A et al (1996) Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins. Cancer Res 56:2355–2360

    PubMed  CAS  Google Scholar 

  9. Gronlund-Pakkanen S, Wahlfors J, Talja M et al (2003) The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma. BJU Int 92:125–130

    Article  PubMed  CAS  Google Scholar 

  10. Huang YY, Tanaka M, Vecchio D et al (2012) Photodynamic therapy induces an immune response against a bacterial pathogen. Expert Rev Clin Immunol 8:479–494

    Article  PubMed  CAS  Google Scholar 

  11. Jocham D, Beer M, Baumgartner R et al (1989) Long-term experience with integral photodynamic therapy of TIS bladder carcinoma. CIBA Found Symp 146:198–208

    PubMed  CAS  Google Scholar 

  12. Jocham D, Wietersheim J von, Pfluger H et al (2009) BCG versus photodynamic therapy (PDT) for nonmuscle invasive bladder cancer-a multicentre clinical phase III study. Aktuelle Urol 40:91–99

    Article  PubMed  CAS  Google Scholar 

  13. Kausch von Schmeling I (2010) Diagnosis of and therapy for non-muscle-invasive bladder cancer – state of the art. Aktuelle Urol 41:307–315

    Article  Google Scholar 

  14. Lee LS, Thong PS, Olivo M et al (2010) Chlorin e6-polyvinylpyrrolidone mediated photodynamic therapy – a potential bladder sparing option for high risk non-muscle invasive bladder cancer. Photodiagnosis Photodyn Ther 7:213–220

    Article  PubMed  CAS  Google Scholar 

  15. Lopez-Beltran A, Montironi R (2004) Non-invasive urothelial neoplasms: according to the most recent WHO classification. Eur Urol 46:170–176

    Article  PubMed  Google Scholar 

  16. Madar-Balakirski N, Tempel-Brami C, Kalchenko V et al (2010) Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with Tookad. PLoS One 5:e10282

    Article  PubMed  Google Scholar 

  17. Mi QW, Cao ZG, Jia T et al (2005) Effect of photodynamic therapy with metalloporphyrin compound on human prostate cancer PC-3 cells in vitro. Zhonghua Nan Ke Xue 11:124–129

    PubMed  CAS  Google Scholar 

  18. Miyazaki K, Morimoto Y, Nishiyama N et al (2012) A novel homogeneous irradiation fiber probe for whole bladder wall photodynamic therapy. Lasers Surg Med 44:413–420

    Article  PubMed  Google Scholar 

  19. Nseyo UO (1996) Photodynamic therapy in the management of bladder cancer. J Clin Laser Med Surg 14:271–280

    PubMed  CAS  Google Scholar 

  20. Nseyo UO, DeHaven J, Dougherty TJ et al (1998) Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience. J Clin Laser Med Surg 16:61–68

    PubMed  CAS  Google Scholar 

  21. Oertel M, Schastak SI, Tannapfel A et al (2003) Novel bacteriochlorine for high tissue-penetration: photodynamic properties in human biliary tract cancer cells in vitro and in a mouse tumour model. J Photochem Photobiol B 71:1–10

    Article  PubMed  CAS  Google Scholar 

  22. Schastak S (2010) Experimentelle Untersuchungen zur minimal-invasiven photodynamischen Therapie von Tumoren und antibiotika-resistenten Bakterien. Habilitationsschrift, Medizinische Fakultät, Universität Leipzig, S 1–123

  23. Schastak S, Jean B, Handzel R et al (2005) Improved pharmacokinetics, biodistribution and necrosis in vivo using a new near infra-red photosensitizer: tetrahydroporphyrin tetratosylat. J Photochem Photobiol B 78:203–213

    Article  PubMed  CAS  Google Scholar 

  24. Schastak S, Yafai Y, Geyer W et al (2008) Initiation of apoptosis by photodynamic therapy using a novel positively charged and water-soluble near infra-red photosensitizer and white light irradiation. Methods Find Exp Clin Pharmacol 30:17–23

    Article  PubMed  CAS  Google Scholar 

  25. Skyrme RJ, French AJ, Datta SN et al (2005) A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma. BJU Int 95:1206–1210

    Article  PubMed  CAS  Google Scholar 

  26. Stenzl A, Cowan NC, De Santis M et al (2011) Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol 59:1009–1018

    Article  PubMed  CAS  Google Scholar 

  27. Tan IB, Dolivet G, Ceruse P et al (2010) Temoporfin-mediated photodynamic therapy in patients with advanced, incurable head and neck cancer: a multicenter study. Head Neck 32:1597–1604

    Article  PubMed  Google Scholar 

  28. Walther MM, Delaney TF, Smith PD et al (1997) Phase I trial of photodynamic therapy in the treatment of recurrent superficial transitional cell carcinoma of the bladder. Urology 50:199–206

    Article  PubMed  CAS  Google Scholar 

  29. Yavari N, Andersson-Engels S, Segersten U, Malmstrom PU (2011) An overview on preclinical and clinical experiences with photodynamic therapy for bladder cancer. Can J Urol 18:5778–5786

    PubMed  Google Scholar 

  30. Zheng JC, Zhao H, Chen B et al (2005) Effect of new photosensitizer CDHS801-mediated photodynamic therapy on bladder cancer: an experimental study. Zhonghua Yi Xue Za Zhi 85:1762–1765

    PubMed  CAS  Google Scholar 

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Danksagung

Dieses Forschungsprojekt wird gefördert von der Deutschen Forschungsgemeinschaft (NE 425/6-1; SCHA 791/3-1). Wir danken Frau Annett Weimann für die exzellente technische Unterstützung.

Einhaltung ethischer Richtlinien

Interessenkonflikt. J. Neuhaus, S. Schastak, M. Berndt, J. Walther, A. Dietel, N. Sieger und J.-U. Stolzenburg geben an, dass kein Interessenkonflikt besteht. Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

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Authors and Affiliations

  1. Department für Operative Medizin, Klinik und Poliklinik für Urologie, Universitätsklinikum Leipzig AöR, Liebigstraße 20, 04103, Leipzig, Deutschland

    J. Neuhaus, M. Berndt, A. Dietel, N. Sieger & J.-U. Stolzenburg

  2. Department für Kopf- und Zahnmedizin, Klinik für Augenheilkunde, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland

    S. Schastak & J. Walther

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  1. J. Neuhaus
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  2. S. Schastak
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  3. M. Berndt
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  4. J. Walther
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  5. A. Dietel
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  6. N. Sieger
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  7. J.-U. Stolzenburg
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Correspondence to J. Neuhaus.

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Neuhaus, J., Schastak, S., Berndt, M. et al. Die photodynamische Therapie des Harnblasenkarzinoms. Urologe 52, 1225–1232 (2013). https://doi.org/10.1007/s00120-013-3306-2

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  • DOI: https://doi.org/10.1007/s00120-013-3306-2

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