Comparison of different treatment schemes in 5-ALA interstitial photodynamic therapy for high-grade glioma in a preclinical model: An MRI study.

Abstract

BACKGROUND\nThere is currently no therapy that prevents high-grade glioma recurrence. Thus, these primary brain tumors have unfavorable outcomes. Recently, 5-ALA photodynamic therapy (PDT) has been proposed to delay relapse and is highly expected to have potential synergistic effects with the current standard of care. However, PDT treatment delivery needs to be optimized by evaluating the impact of both the number of fractions and the light power used.\n\n\nOBJECTIVES\nPrevious studies have reported MRI examination-based outcomes for PDT in glioblastoma. Our study aimed to compare MRI markers across different treatment schemes that use interstitial PDT in high-grade glioma in a preclinical model.\n\n\nMATERIALS AND METHODS\nForty-eight nude rats were grafted with human U87 cells into the right putamen and subsequently submitted to interstitial PDT. The rats were randomized into six groups, including two different sham groups and four different treated groups (5 fractions at 5\u2009mW or 30\u2009mW and 2 fractions at 5\u2009mW or 30\u2009mW). After photosensitizer (PS) precursor (5-ALA) intake, an optical fiber was introduced into the tumor. Treatment effects were assessed with early high-field MRI to acquire T1 and T2 diffusion and perfusion images.\n\n\nRESULTS\nThere was no difference in the variation of the diffusion coefficient among the six groups (p\u2009=\u20090.0549, Kruskal-Wallis test). However, a significant difference was identified among the six groups in terms of variation in perfusion (p\u2009=\u20090.048, Kruskal-Wallis test), supporting a lesional effect in the treated groups. Additionally, the sham groups had significantly smaller edema volumes than were observed in the treated groups. Moreover, the 5-fraction group treated with 30\u2009mW was associated with edema volumes that were significantly greater than those in the 5-fraction group treated with 5\u2009mW (p\u2009=\u20090.019).\n\n\nCONCLUSION\nBased on observations of MRI data and considering treatment effects, the 5-fraction group treated at 5\u2009mW was not significantly different from the other treated groups in terms of cell deaths, characterized by diffusion imaging, or necrosis level. However, the significantly lower level of edema observed in this group indicated that this treatment scheme had limited toxicity.