Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, Hokkaido, Japan.
J Nucl Med. 2013 Jul;54(7):1060-5. doi: 10.2967/jnumed.112.114355. Epub 2013 May 22.
Hypoxia is a common feature of cancer and a prognostic factor for many types of cancer. (18)F-fluoromisonidazole ((18)F-FMISO) PET can detect tumor hypoxia noninvasively. Hypoxia-inducible factor-1 (HIF-1) is a key player in the transcriptional response to low oxygen tension in many types of cancer. Its activity is mainly dependent on the stability and modification of HIF-1α, which is a composition of HIF-1. However, it is unclear whether (18)F-FMISO PET can identify HIF-1α expression in oral squamous cell carcinoma (OSCC). The present study was performed to elucidate the correlation between (18)F-FMISO PET findings and HIF-1α expression in OSCC.
Twenty-three patients (age range, 42-84 y; 15 men, 8 women) with OSCC were enrolled in this study. The T-stages of cancer were T1 in 1 patient, T2 in 9, T3 in 2, and T4a in 11. The N-stages were N0 in 13 patients, N1 in 5, and N2 in 5. Each patient underwent (18)F-FMISO and (18)F-FDG PET before surgery, and the maximum standardized uptake value (SUV max) of both PET studies was measured. HIF-1α expression in the operation materials was evaluated by immunohistochemical staining. The SUV max of both PET studies and HIF-1α findings were compared statistically.
(18)F-FMISO PET detected uptake in the primary site in 14 of the 23 patients (61%). The median SUV max of (18)F-FMISO and (18)F-FDG PET in the primary site was 1.83 (range, 0.8-2.7) and 16.5 (range, 1.0-32.3), respectively. There was a weak significant correlation between (18)F-FMISO and (18)F-FDG PET SUV max (P = 0.02, r = 0.48). HIF-1α expression was clearly detected in 11 of the 23 patients (48%). The (18)F-FMISO PET SUV max was significantly higher in the HIF-1α-positive cases than in the HIF-1α-negative cases (median, 2.1; range, 1.5-2.4, vs. median, 1.6; range, 0.8-2.0, respectively) (P = 0.002). However, there were no significant correlations between (18)F-FDG PET SUV max and HIF-1α expression (median, 21.8; range, 7.7-29.1 vs. 1.0-32.2) (P = 0.06).
(18)F-FMISO uptake in the primary site of OSCC indicates a hypoxic environment with HIF-1α expression.
阐明口腔鳞状细胞癌（OSCC）中（18）F-氟代单唾液酸神经节苷脂（（18）F-FMISO）正电子发射断层扫描（PET）摄取与缺氧诱导因子-1α（HIF-1α）表达之间的相关性。
本研究纳入了 23 例 OSCC 患者（年龄 42-84 岁；男 15 例，女 8 例）。癌症的 T 分期为 T1 期 1 例，T2 期 9 例，T3 期 2 例，T4a 期 11 例。N 分期为 N0 期 13 例，N1 期 5 例，N2 期 5 例。每位患者均在术前接受（18）F-FMISO 和（18）F-FDG PET 检查，并测量了两种 PET 研究的最大标准化摄取值（SUVmax）。采用免疫组织化学染色法评估手术标本中的 HIF-1α 表达情况。对两种 PET 研究的 SUVmax 和 HIF-1α 结果进行统计学比较。
（18）F-FMISO PET 在 23 例患者中的 14 例（61%）原发性肿瘤部位检测到摄取。原发性肿瘤部位（18）F-FMISO 和（18）F-FDG PET 的 SUVmax 中位数分别为 1.83（范围，0.8-2.7）和 16.5（范围，1.0-32.3）。（18）F-FMISO 和（18）F-FDG PET SUVmax 之间存在弱显著相关性（P=0.02，r=0.48）。在 23 例患者中有 11 例（48%）明确检测到 HIF-1α 表达。HIF-1α 阳性病例的（18）F-FMISO PET SUVmax 明显高于 HIF-1α 阴性病例（中位数分别为 2.1（范围，1.5-2.4）和 1.6（范围，0.8-2.0）（P=0.002）。然而，（18）F-FDG PET SUVmax 与 HIF-1α 表达之间无显著相关性（中位数分别为 21.8（范围，7.7-29.1）和 1.0-32.2）（P=0.06）。
OSCC 原发灶的（18）F-FMISO 摄取表明存在缺氧环境，伴有 HIF-1α 表达。
