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

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, T₂-weighted and CEST MRI were performed over 7 days.
Results: We observed that rePDT resulted in a continuous suppression of tumors according to T₂-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.
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