title: In vivo fluence rate and fractionation effects on tumor response and photobleaching: photodynamic therapy with two photosensitizers in an orthotopic rat tumor model.
abstract: The effect of fluence rate and light fractionation on phototoxicity was investigated in vivo in an orthotopic rat bladder tumor model. Two photosensitizers, benzoporphyrin derivative monoacid ring A and 5-aminolevulinic acid-induced protoporphyrin IX, were studied. For a given cumulative light dose of 30 J/cm2, enhanced tumor destruction was observed from both photosensitizers when using either lower fluence rates or fractionated light delivery. Photobleaching experiments in vivo demonstrated that the photobleaching rate, however, was not fluence rate dependent. The fluence rate and light fractionation effects on tumor phototoxicity lead to rapid local depletion in oxygen concentration that inhibited subsequent photochemical reactions necessary for efficient photodestruction of tumor cells. Nicotinamide did not enhance photodynamic therapy efficacy, suggesting that the added increase of oxygen within the tumor was not sufficient to enhance photodestruction of hypoxic cell fractions. The independence of the photobleaching rate with fluence rate suggests distinct mechanisms, at least in part, of photodestruction of the tumor and the photosensitizer and that the rate of photosensitizer photo-bleaching may not always be an appropriate monitor for singlet oxygen availability and photodynamic therapy dosimetry.
authors.affiliation: Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
authors.forename: S
authors.initials: S
authors.lastname: Iinuma
authors.forename: K T
authors.initials: KT
authors.lastname: Schomacker
authors.forename: G
authors.initials: G
authors.lastname: Wagnieres
authors.forename: M
authors.initials: M
authors.lastname: Rajadhyaksha
authors.forename: M
authors.initials: M
authors.lastname: Bamberg
authors.forename: T
authors.initials: T
authors.lastname: Momma
authors.forename: T
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D017484:Dermatitis, Phototoxic; D004195:Disease Models, Animal; D005260:Female; D008027:Light; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D009536:Niacinamide; D000622:Aminolevulinic Acid