Imaging treatment efficacy of repeated photodynamic therapy in glioblastoma using chemical exchange transfer saturation MRI

Abstract Purpose To observe the tumor responses during photodynamic therapy in a murine glioblastoma model using chemical exchange saturation transfer (CEST) MRI and to compare the treatment effectiveness between single photodynamic therapy (sPDT) and repeated PDT (rePDT). Methods After tumor cell implantation in NSG mouse brain ( n = 27), mice were subjected to four PDT sessions (rePDT), sPDT after the administration of 5‐aminolevulinic acid 6 h before each session, and a non‐PDT session (control). A 630‐nm LED light was used to effectuate PDT. After 24 h for each PDT session, T 2 ‐weighted and CEST MRI were performed over 7 days. Results We observed that rePDT resulted in a continuous suppression of tumors according to T 2 ‐weighted images; thus, the tumor volume was the smallest among three groups on Day 7. Both CEST contrasts at 3.5 ppm (amide proton transfer, APT) and 3.5 ppm (relayed nuclear Overhauser enhancement, rNOE) in the rePDT group were significantly lower ( p < 0.05) than those in the control group starting from Day 5, which corresponds to lower protein and cellularity in tumors in the rePDT group, respectively. CEST contrast decreased by 17.9% at 3.5 ppm and 11.3% at 3.5 ppm for rePDT group. This was validated by histology, where we observed moderate correlations between APT with cell proliferation ( R = 0.730, p < 0.01) and cell apoptosis ( R = 0.715, p < 0.05) and moderate correlation between rNOE with cellularity (R = 0.796, p < 0.01). Conclusions rePDT has a better effect in tumor growth suppression when compared with sPDT, and CEST could be a robust and noninvasive mean to assess the molecular changes related to treatment efficacy.