Hypoxia-imaging with 18F-Misonidazole and PET: Changes of kinetics during radiotherapy of head-and-neck cancer

Abstract Background and purpose PET with 18 F-Misonidazole (FMISO-PET) is a non-invasive method for measuring tumor hypoxia. We analysed changes of FMISO-uptake during radiotherapy and their impact on patient outcome. Materials and methods Fourteen patients with HNC underwent repeated FMISO-PET prior to radiotherapy and after 30Gy. Dynamic and static PET-scans (2+4h p.i.) were acquired. FMISO-uptake was quantified by calculating standard uptake values (SUV) and tumor-muscle-ratios (TMR). Kinetic curve types representing tissue hypoxia were defined. Change of curve type was correlated with patient outcome. Results The mean SUV 4h p.i. and the TMR decreased significantly during radiotherapy. SUV decreased clearly in 12/14 patients, and increased in 2 patients. TMR decreased in 11 patients, and increased in 3 patients. Prior to radiotherapy, three different shapes of kinetic curve types indicative for the degree of hypoxia could be defined in 12/14 patients: (1) accumulation type (severe hypoxia ( n =8)), (2) intermediate type (intermediate degree of hypoxia ( n =3)), and (3) wash-out type (low degree of hypoxia ( n =1)). Curve type changed towards a lower degree of hypoxia at 30Gy in all but 3 patients. In three patients curve type remained unchanged. Conclusions The changes in tumor FMISO-uptake during radiotherapy indicate radio-induced reoxygenation.

[1]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[2]  H. Machulla,et al.  Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters , 1999 .

[3]  K L Lindsley,et al.  Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. , 1995, International journal of radiation oncology, biology, physics.

[4]  M. Dewhirst,et al.  Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. , 1996, Cancer research.

[5]  C. Koch,et al.  2-Nitroimidazole (EF5) binding predicts radiation resistance in individual 9L s.c. tumors. , 1996, Cancer research.

[6]  J. Eary,et al.  [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  T K Lewellen,et al.  Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. , 1996, International journal of radiation oncology, biology, physics.

[8]  Matthias Reimold,et al.  Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  P Vaupel,et al.  Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  M. Dewhirst,et al.  Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. , 1997, International journal of radiation oncology, biology, physics.

[11]  I. Olivotto,et al.  Gel electrophoresis of individual cells to quantify hypoxic fraction in human breast cancers. , 1993, Cancer research.

[12]  P. Olive,et al.  Hypoxic fractions measured in murine tumors and normal tissues using the comet assay. , 1994, International journal of radiation oncology, biology, physics.