title: Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours.
abstract: OBJECTIVE
  To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex-vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer. Materials and methods The study included 11 cystectomy specimens containing invasive TCC (five from patients who had previously received external-beam bladder radiotherapy, but with recurrent TCC) and three 'normal' bladders removed from patients treated by exenteration surgery for extravesical pelvic cancer. Full-thickness bladder wall and tumour samples were taken from these specimens and using an 'intravesical' and a previously validated interstitial model, the optical penetration depths (i.e. the tissue depth at which the light fluence is 37% of incident) were calculated at wavelengths of 633, 673 and 693 nm.
  
  
  RESULTS
  There were no significant differences in light penetration between normal and tumour-affected bladder tissue at each wavelength. There were significant differences in light penetration among wavelengths; light at 693 nm penetrated approximately 40% further than light at 633 nm (P < 0.002). The light currently used in bladder PDT (633 nm) has a mean (SEM) optical penetration depth of 4.0 (0.1) mm within TCC. In addition, at this wavelength, there was 29% greater light penetration in previously irradiated than in unirradiated bladder wall (P = 0.001). This did not occur in the tumour-affected bladder.
  
  
  CONCLUSIONS
  Bladder tissue is relatively more translucent than other human tissues and there is therefore great potential for PDT in the treatment of bladder cancer. As there is no difference in light penetration between TCC and normal bladder tissue, a tumour-specific response with diffuse illumination of the bladder will depend on drug localization within the tumour. The currently used wavelength of 633 nm can be expected to exert a PDT effect within bladder tumour up to a depth of 20 mm. Increasing the wavelength will allow deeper pathology to be treated.
authors.affiliation: Paterson Institute for Cancer Research, Christie Hospital, Departments of Urology, Hope Hospital, Salford Royal Hospitals Trust, Salford, South Manchester University Hospital, and Christie Hospital, Manchester, UK.
authors.forename: D C
authors.initials: DC
authors.lastname: Shackley
authors.forename: C
authors.initials: C
authors.lastname: Whitehurst
authors.forename: J V
authors.initials: JV
authors.lastname: Moore
authors.forename: N J
authors.initials: NJ
authors.lastname: George
authors.forename: C D
authors.initials: CD
authors.lastname: Betts
authors.forename: N W
authors.initials: NW
authors.lastname: Clarke
mesh_terms: D006801:Humans; D008027:Light; D010778:Photochemotherapy / Q000379:methods*; D001743:Urinary Bladder / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*