How to Avoid Local Side Effects of Bladder Photodynamic Therapy: Impact of the Fluence Rate
Abstract
Purpose:
We studied how to avoid irritative bladder symptoms after bladder photodynamic therapy, such as urgency, frequency and pain, which are associated with the inflammation and destruction of normal urothelium.
Materials and Methods:
Rats bearing orthotopic bladder tumors were instilled with hexyl-aminolevulinate and illuminated with red light at a high vs low (100 vs 15 mW/cm2) fluence rate. Cystectomy specimens 48 hours after treatment were subjected to anatomopathological examination. Inflammatory reaction and apoptosis were evaluated. In vivo photobleaching was assessed during illumination at each fluence rate.
Results:
All superficial tumors were eradicated irrespective of light dose and fluence rate. High fluence rates induced necrosis with inflammatory reaction and absent normal urothelium. Low fluence rates did not provoke inflammation and resulted in apoptotic cell death with preserved urothelial integrity. This could be attributable to faster photobleaching of the photosensitizer in normal urothelium at low fluence rates.
Conclusions:
Bladder photodynamic therapy at a low fluence rate minimizes side effects without hampering therapeutic efficacy.
References
- 1 : Photodynamic applications in superficial bladder cancer: facts and hopes!. J Environ Pathol Toxicol Oncol2006; 25: 441. Google Scholar
- 2 : Long-term results of whole bladder wall photodynamic therapy for carcinoma in situ of the bladder. Urology1995; 45: 763. Google Scholar
- 3 : New optical imaging technologies for bladder cancer: considerations and perspectives. J Urol2012; 188: 361. Link, Google Scholar
- 4 : Photodynamic therapy for superficial bladder cancer under local anaesthetic. BJU Int2002; 89: 665. Google Scholar
- 5 : Photodynamic therapy with intravesical instillation of 5-aminolevulinic acid for patients with recurrent superficial bladder cancer: a single-center study. Urology2003; 61: 338. Google Scholar
- 6 : A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma. BJU Int2005; 95: 1206. Google Scholar
- 7 : Whole bladder photodynamic therapy with 5-aminolevulinic acid using a white light source. Urology2003; 61: 332. Google Scholar
- 8 : Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome. Br J Dermatol2004; 151: 1204. Google Scholar
- 9 : Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic-acid photodynamic therapy. J Invest Dermatol2006; 126: 2679. Google Scholar
- 10 : Hexyl-aminolevulinate-mediated photodynamic therapy: how to spare normal urothelium. An in vitro approach. Lasers Surg Med2007; 39: 67. Google Scholar
- 11 : Kinetics, biodistribution and therapeutic efficacy of hexylester 5-aminolevulinate induced photodynamic therapy in an orthotopic rat bladder tumor model. J Urol2004; 172: 2013. Link, Google Scholar
- 12 : Analysis of differential PDT effect in rat bladder tumor models according to concentrations of intravesical hexyl-aminolevulinate. Photochem Photobiol Sci2008; 7: 1018. Google Scholar
- 13 : Characterization of a novel transplantable orthotopic rat bladder transitional cell tumour model. Br J Cancer1999; 81: 638. Google Scholar
- 14 : Assessment of apoptosis by immunohistochemistry to active caspase-3, active caspase-7, or cleaved PARP in monolayer cells and spheroid and subcutaneous xenografts of human carcinoma. J Histochem Cytochem2009; 57: 289. Google Scholar
- 15 : Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin. Int J Oncol2006; 28: 775. Google Scholar
- 16 : Acute effects of combined photodynamic therapy and hyperbaric oxygenation in lung cancer—a clinical pilot study. Lasers Surg Med2001; 28: 399. Google Scholar
- 17 : Effect of irradiation fluence rate on the efficacy of photodynamic therapy and tumor oxygenation in meta-tetra (hydroxyphenyl) chlorin (mTHPC)-sensitized HT29 xenografts in nude mice. Radiat Res2002; 158: 339. Google Scholar
- 18 : Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas. Clin Cancer Res2008; 14: 4475. Google Scholar
- 19 : Bradykinin and peripheral sensitization. Biol Chem2006; 387: 11. Google Scholar
- 20 : The use of the isolated mouse whole bladder for investigating bladder overactivity. J Pharmacol Exp Ther2006; 319: 1386. Google Scholar
- 21 : Compartmental targeting for mTHPC-based photodynamic treatment in vivo: correlation of efficiency, pharmacokinetics, and regional distribution of apoptosis. Int J Radiat Oncol Biol Phys2010; 78: 563. Google Scholar
- 22 : Necrotic and apoptotic features of cell death in response to Foscan photosensitization of HT29 monolayer and multicell spheroids. Biochem Pharmacol2005; 69: 1167. Google Scholar
- 23 : The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol1998; 159: 1862. Link, Google Scholar
