Advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with oral squamous cell carcinoma

  • Jun Sato
  • Yoshimasa Kitagawa
  • Yutaka Yamazaki
  • Hironobu Hata
  • Takuya Asaka
  • Masaaki Miyakoshi
  • Shozo Okamoto
  • Tohru Shiga
  • Masanobu Shindoh
  • Yuji Kuge
  • Nagara Tamaki
Original Article



Hypoxia, a prognostic factor in many types of cancer, can be detected by 18F-fluoromisonidazole (FMISO) positron emission tomography (PET). It is unclear whether hypoxia reflects the response to chemotherapy in patients with oral squamous cell carcinoma (OSCC). The correlations of FMISO-PET and FDG-PET with histological response to preoperative chemotherapy were therefore assessed in patients with OSCC.


This study enrolled 22 patients with OSCC undergoing preoperative chemotherapy. The T-stages were T2 in 6 patients, T3 in 3, and T4a in 13, and the N-stages were N0 in 14 patients, N1 in 3, and N2 in 5. Each patient was evaluated by both FMISO-PET and FDG-PET before surgery, and the maximum standardized uptake value (SUVmax) of FDG- and FMISO-PET and tumor-muscle ratio (TMR) of FMISO-PET were measured. The threshold for the hypoxic volume based on TMR was set at 1.25. The histological response to preoperative chemotherapy was evaluated using operative materials.


FMISO-PET and FDG-PET detected uptake by primary OSCCs in 15 (68 %) and 21 (95 %) patients, respectively, and median SUVmaxs of FMISO- and FDG-PET in the primary site were 2.0 (range, 1.3–3.5) and 16.0 (range, 1.0–32.2), respectively. The median of FMISO TMR was 1.5 (range, 0.99–2.96). There were five cases whose FMISO TMR was less than 1.25. Histological evaluation showed good response to preoperative chemotherapy in 7 patients (32 %) and poor response in 15 (68 %). Good response was significantly more prevalent in patients with negative than positive FMISO uptake (P < 0.001) and without the hypoxic area evaluated by FMISO-PET TMR (P = 0.04), whereas FDG uptake was not significantly correlated with response to chemotherapy response. Multivariate logistic regression analysis showed that FMISO uptake was an independent significant predictor of response to preoperative chemotherapy (P = 0.03, odds ratio = 0.06, 95 % confidence interval = 0.004–0.759).


An advantage of FMISO-PET over FDG-PET for predicting histological response to preoperative chemotherapy in patients with OSCC was observed.


Hypoxia FMISO-PET FDG-PET Preoperative chemotherapy HIF-1α Oral squamous cell carcinoma 



This study was partially supported by a Grant-in-Aid for Scientific Research (2010–2011: 22592203).

Conflict of interest

None of the authors of this manuscript has any financial relationship with any organization, or any conflict of interest, regarding this study.

Supplementary material

259_2014_2810_MOESM1_ESM.ppt (47 kb)
Supplementary figure 1 TMR of FMISO-PET or SUV max of FDG-PET and response to chemotherapy in nine patients who received PET examination before chemotherapy. White and black circles indicate patients having tumors without (n = 2) and with (n = 7) FMISO uptake, respectively. Dotted circles indicate the seven patients who showed good histological response to preoperative chemotherapy (PPT 47 kb)
259_2014_2810_MOESM2_ESM.ppt (50 kb)
Supplementary figure 2 TMR of FMISO-PET or SUV max of FDG-PET and response to chemotherapy in 13 patients who received PET examination after initiating chemotherapy. White and black circles indicate patients having tumors without (n = 5) and with (n = 8) FMISO uptake, respectively. Dotted circles indicate the seven patients who showed good histological response to preoperative chemotherapy (PPT 50 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jun Sato
    • 1
  • Yoshimasa Kitagawa
    • 1
  • Yutaka Yamazaki
    • 1
  • Hironobu Hata
    • 1
  • Takuya Asaka
    • 1
  • Masaaki Miyakoshi
    • 1
  • Shozo Okamoto
    • 2
  • Tohru Shiga
    • 2
  • Masanobu Shindoh
    • 3
  • Yuji Kuge
    • 4
  • Nagara Tamaki
    • 2
  1. 1.Oral Diagnosis and Medicine, Department of Oral Pathobiological Science, Graduate School of Dental MedicineHokkaido UniversitySapporoJapan
  2. 2.Department of Nuclear Medicine, Graduate School of MedicineHokkaido UniversitySapporoJapan
  3. 3.Department of Oral Pathology & BiologyHokkaido University Graduate School of Dental MedicineSapporoJapan
  4. 4.Central Institute of Isotope ScienceHokkaido UniversitySapporoJapan

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