Predictive value of (18)F-FAZA PET imaging for guiding the association of radiotherapy with nimorazole: a preclinical study

Radiother Oncol. 2015 Feb;114(2):189-94. doi: 10.1016/j.radonc.2014.12.015. Epub 2015 Jan 20.

Abstract

Purpose: To assess the predictive value of hypoxia imaging by (18)F-FAZA PET in identifying tumors that may benefit from radiotherapy combined with nimorazole, a hypoxic radiosensitizer.

Material and methods: Rats of two tumor models (Rhabdomyosarcoma and 9L-glioma) were divided into two treated groups: radiotherapy (RT) alone or RT plus nimorazole. (18)F-FAZA PET images were obtained to evaluate tumor hypoxia before the treatment. Treatment outcome was assessed through the tumor growth time assay, defined as the time required for tumor to grow to 1.5 times its size before irradiation.

Results: For rhabdomyosarcomas, the benefit of adding nimorazole to RT was not significant when considering all tumors. When stratifying into more and less hypoxic tumors according to the median (18)F-FAZA T/B ratio, we found that the combined treatment significantly improved the response of the "more hypoxic" subgroup, while there was no significant difference in the tumor growth time between the two treatment modalities for the "less hypoxic" subgroup. For 9L-gliomas, a clear benefit was demonstrated for the group receiving RT+nimorazole. However, the individual responses within the RT+nimorazole group were highly variable and independent of the (18)F-FAZA uptake.

Conclusions: (18)F-FAZA PET may be useful to guide hypoxia-directed RT using nimorazole as radiosensitizer. It identified a subgroup of more hypoxic tumors (displaying T/B ratio>2.72) that would benefit from this combined treatment. Nevertheless, the predictive power was limited to rhabdomyosarcomas and ineffective for 9L-gliomas.

Keywords: (18)F-FAZA; Hypoxia; Nimorazole; Predictive marker; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia / physiology
  • Chemoradiotherapy
  • Disease Models, Animal
  • Fluorine Radioisotopes
  • Glioma / diagnostic imaging*
  • Glioma / drug therapy
  • Glioma / radiotherapy
  • Glioma / therapy*
  • Male
  • Nimorazole / pharmacology*
  • Nitroimidazoles*
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Rhabdomyosarcoma / diagnostic imaging*
  • Rhabdomyosarcoma / drug therapy
  • Rhabdomyosarcoma / radiotherapy
  • Rhabdomyosarcoma / therapy*

Substances

  • Fluorine Radioisotopes
  • Nitroimidazoles
  • Radiopharmaceuticals
  • fluoroazomycin arabinoside
  • Nimorazole