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., MD, Colin, P., MD, Betrouni, N., PhD, Maurage, C.A., MD, PhD, Leroy, X., MD, PhD, Simonin, S, Martin-Schmitt, C., MD, Villers, A., MD, PhD, Mordon, S., PhD
• 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
• DOI: 10.1016/j.pdpdt.2013.01.003

Summary Objectives To evaluate photodynamic therapy (PDT) using 5-ALA-induced protoporphyrin IX (PPIX) in an in vivo hypoxic tumor model and its monitoring using MRI. Materiel and 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/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. 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. Conclusion 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.