title: Efficiency of 5-ALA mediated photodynamic therapy on hypoxic prostate cancer: a preclinical study on the Dunning R3327-AT2 rat tumor model.
abstract: OBJECTIVE
  To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI.
  
  
  METHODS
  Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150 mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633 nm; fluence=100 J/cm(2)). MRI at baseline and 2 days after treatment (T1, T2 and dynamic gadolinium enhanced sequences) were performed. Necrosis volumes were determined on post-procedure MRI. Tumors were resected 2 days post-PDT and obtained necrosis was determined histopathologically. Intra-tumoral PPIX distribution was evaluated using confocal microscopy and tissue porphyrin quantification.
  
  
  RESULTS
  Twenty rats were treated divided into three groups: continuous (n=7), fractionated illumination (n=7), and a control group receiving only light or only ALA or neither (n=6). Baseline MRI confirmed the hypoxic character of tumors. Necrosis volumes determined on posttreatment MRI were not reproducible and presented with important geometric and volumetric variability. Average necrosis volumes of 0.39 cc (0-0.874 cc) in the continuous group, 0.24 cc (0.107-0.436 cc) in the fractionated group and 0.012 cc (0-0.071 cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration.
  
  
  CONCLUSIONS
  Necrosis volumes induced by 5-ALA-mediated PDT were highly variable and non reproducible, probably because of lack of intra-tissular oxygen. Photosensitizer was poorly represented inside the tumor and its distribution was heterogeneous. Our study suggests that 5-ALA-mediated PDT might not be the best management option for hypoxic prostatic adenocarcinoma.
authors.affiliation: Lille University Hospital, Department of Urology, France. bozzini_gregory@yahoo.fr
authors.forename: G
authors.initials: G
authors.lastname: Bozzini
authors.forename: P
authors.initials: P
authors.lastname: Colin
authors.forename: N
authors.initials: N
authors.lastname: Betrouni
authors.forename: C A
authors.initials: CA
authors.lastname: Maurage
authors.forename: X
authors.initials: X
authors.lastname: Leroy
authors.forename: S
authors.initials: S
authors.lastname: Simonin
authors.forename: C
authors.initials: C
authors.lastname: Martin-Schmitt
authors.forename: A
authors.initials: A
authors.lastname: Villers
authors.forename: S
authors.initials: S
authors.lastname: Mordon
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination / Q000379:methods; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011524:Protoporphyrins / Q000008:administration & dosage*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-ALA; Photodynamic therapy; Preclinical; Prostate cancer