title: Irradiance-dependent photobleaching and pain in delta-aminolevulinic acid-photodynamic therapy of superficial basal cell carcinomas.
abstract: OBJECTIVE
  In superficial basal cell carcinomas treated with photodynamic therapy with topical delta-aminolevulinic acid, we examined effects of light irradiance on photodynamic efficiency and pain. The rate of singlet-oxygen production depends on the product of irradiance and photosensitizer and oxygen concentrations. High irradiance and/or photosensitizer levels cause inefficient treatment from oxygen depletion in preclinical models.
  
  
  METHODS
  Self-sensitized photobleaching of protoporphyrin IX (PpIX) fluorescence was used as a surrogate metric for photodynamic dose. We developed instrumentation measuring fluorescence and reflectance from lesions and margins during treatment at 633 nm with various irradiances. When PpIX was 90% bleached, irradiance was increased to 150 mW/cm(2) until 200 J/cm(2) were delivered. Pain was monitored.
  
  
  RESULTS
  In 33 superficial basal cell carcinomas in 26 patients, photobleaching efficiency decreased with increasing irradiance above 20 mW/cm(2), consistent with oxygen depletion. Fluences bleaching PpIX fluorescence 80% (D80) were 5.7 +/- 1.6, 4.5 +/- 0.3, 7.5 +/- 0.8, 7.4 +/- 0.3, 12.4 +/- 0.3, and 28.7 +/- 7.1 J/cm(2), respectively, at 10, 20, 40, 50, 60 and 150 mW/cm(2). At 20-150 mW/cm(2), D80 doses required 2.5-3.5 min; times for the total 200 J/cm(2) were 22.2-25.3 min. No significant pain occurred up to 50 mW/cm(2); pain was not significant when irradiance then increased. Clinical responses were comparable to continuous 150 mW/cm(2) treatment.
  
  
  CONCLUSIONS
  Photodynamic therapy with topical delta-aminolevulinic acid using approximately 40 mW/cm(2) at 633 nm is photodynamically efficient with minimum pain. Once PpIX is largely photobleached, higher irradiances allow efficient, rapid delivery of additional light. Optimal fluence at a single low irradiance is yet to be determined.
authors.affiliation: Department of Imaging Sciences, University of Rochester, Rochester, New York, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Cottrell
authors.forename: Anne D
authors.initials: AD
authors.lastname: Paquette
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Keymel
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Foster
authors.forename: Allan R
authors.initials: AR
authors.lastname: Oseroff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010147:Pain Measurement; D038761:Photobleaching; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX