Efficiency of 5-ALA mediated photodynamic therapy on hypoxic prostate cancer: A preclinical study on the Dunning R3327-AT2 rat tumor model

• Published in: Photodiagnosis and photodynamic therapy Vol. 10; no. 3; pp. 296 - 303
• Main Authors: Bozzini, G., Colin, P., Betrouni, N., Maurage, C.A., Leroy, X., Simonin, S., Martin-Schmitt, C., Villers, A., Mordon, S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2013
• Subjects: 5-ALA; Aminolevulinic Acid - administration & dosage; Animals; Cell Hypoxia; Cell Line, Tumor; Drug Evaluation, Preclinical; Drug Therapy, Combination - methods; Hematology, Oncology and Palliative Medicine; Internal Medicine; Male; Photochemotherapy - methods; Photodynamic therapy; Photosensitizing Agents - therapeutic use; Preclinical; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Protoporphyrins - administration & dosage; Rats; Treatment Outcome; Photodynamic therapy; Preclinical; Prostate cancer; 5-ALA
• ISSN: 1572-1000; 1873-1597; 1873-1597
• DOI: 10.1016/j.pdpdt.2013.01.003

To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. Dunning R3327-AT2 tumors were grafted in the neck of Copenhagen rats. PDT using 150mg 5-ALA/kg i.v. was performed by focal interstitial illumination of the photosensitized tumor (λ=633nm; fluence=100J/cm2). 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. 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 0.39cc (0–0.874cc) in the continuous group, 0.24cc (0.107–0.436cc) in the fractionated group and 0.012cc (0–0.071cc) in the control group were observed. Intra-tumoral PPIX distribution was heterogeneous and PPIX quantification revealed low intra-tumoral concentration. 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.