Evaluation of tumour hypoxia during radiotherapy using [18F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer

Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2139-2146. doi: 10.1007/s00259-016-3429-y. Epub 2016 Jun 1.

Abstract

Background and purpose: Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [18F]HX4-PET, hypoxia-related blood biomarkers, and their interdependence.

Material and methods: [18F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after ±20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [18F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed.

Results: At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7 ± 19.8 % (baseline) to 3.6 ± 10.0 % (during treatment; P < 0.001). Only two patients had a HV > 1 cm3 during treatment, which was located for >98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased.

Conclusions: [18F]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia.

Keywords: CAIX; Hypoxia; Osteopontin; PET; VEGF.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Imidazoles*
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome
  • Triazoles*
  • Tumor Hypoxia / radiation effects*

Substances

  • Biomarkers, Tumor
  • HX4 compound
  • Imidazoles
  • Radiopharmaceuticals
  • Triazoles