18F-Fluoromisonidazole−Positron Emission Tomography and Immunohistochemistry Verified Tumor Oxygenation, Stemness, and Immunosupportive Microenvironment After Preoperative Neoadjuvant Bevacizumab for Newly Diagnosed Glioblastoma

• Published in: World neurosurgery Vol. 175; pp. e1364 - e1374
• Main Authors: Suzuki, Tomoya, Takei, Jun, Fukasawa, Nei, Suzuki, Kenta, Ogawa, Daisuke, Yamamoto, Yohei, Akasaki, Yasuharu, Murayama, Yuichi, Shimoda, Masayuki, Miyake, Keisuke, Tanaka, Toshihide
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-07-2023
• Subjects: FMISO-PET; Glioblastoma; Neoadjuvant bevacizumab; Tumor microenvironment; Tumor oxygenation; TBRmax; TMZ; RT; Tumor microenvironment; TBR; neo-Bev; VEGF; Glioblastoma; TME; HV; Tumor oxygenation; Bev; GBM; Neoadjuvant bevacizumab; FMISO-PET
• ISSN: 1878-8750; 1878-8769; 1878-8769
• DOI: 10.1016/j.wneu.2023.05.030

Cancer stemness and immunosuppressive tumor microenvironment (TME) in accordance with tumor oxygenation are variable during bevacizumab (Bev) therapy for glioblastoma (GBM). Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) reflects hypoxic TME. The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment.
Seven patients with newly diagnosed IDH-wildtype GBM underwent FMISO-PET during follow-up. Three patients received preoperative neoadjuvant Bev (neo-Bev) and subsequently underwent surgical resection. Reoperation was performed at the recurrence. FMISO-PET was performed before and after neo-Bev. Four patients who underwent tumor resection without neo-Bev were included as the control group. Expressions of hypoxic markers (carbonic anhydrase; CA9), stem cell markers (nestin, FOXM1), and immunoregulatory molecules (CD163, FOXP3, PD-L1) in tumor tissues were analyzed by immunohistochemistry (IHC).
All 3 patients treated with neo-Bev showed decrease in FMISO accumulation in accordance with expressions of CA9 and FOXM1 compared with the control group. Two of these 3 patients at the recurrence showed increase in FMISO accumulation. IHC showed increased CA9-and FOXM1-positive cells in recurrent tumors. Expression of PD-L1 tended to be lower after neo-Bev compared with the control group.
FMISO-PET effectively visualized TME oxygenation after neo-Bev. Increased FMISO accumulation at the time of recurrence, even under Bev treatment, suggests that FMISO-PET might be useful for monitoring the duration of Bev efficacy by reflecting tumor oxygenation.