Trial Information

Methodological Evaluation of Fluor 18 Labelled Fluoromisonidazole ([18F]-FMISO) Positon Emission Tomography-Computed Tomography (PET-CT) for Non Operated Glioblastoma

Hypoxia is one of the worst prognostic factors of clinical outcome in glioblastomas. Today,
it is well admitted that hypoxia is heterogeneous, variable within different tumour types
and varied spatially and temporally. Hypoxia induced proteomic and gene expression changes
that lead to increase angiogenesis, invasion and metastasis. So the hypoxic fraction in
solid tumours reduces their sensitivity to conventional treatment modalities, modulating
therapeutic response to ionizing radiation or certain chemotherapeutic agents. This is
particularly important in glioblastomas. Hypoxic cells in solid tumours could influence
local failure following radiotherapy and has been associated with malignant progression,
loco regional spread and distant metastases and represents an increasing probability of
recurrence.

Thus, the non-invasive determination and monitoring of the oxygenation status of tumours is
of importance to classify patients' outcome and modify therapeutic strategies in those
tumours. Actually the oxygenation status of individual tumours is not assessed routinely.
Numerous different approaches have been used to identify hypoxia in tumours. Eppendorf
oxygen probe measurements (pO2 histography) may be considered as a 'gold standard' for
hypoxia in human malignancies. However, it is an invasive method being confined to
superficial, well accessible tumours and requires many measures. PET using
[18F]Fluoro-deoxyglucose ([18F]-FDG), allows non-invasive imaging of glucose metabolism and
takes a growing place in cancer staging, but [18F]-FDG can't assess correctly the
oxygenation status of tumours and is not suitable for brain tumor. PET with appropriate
radiotracers enables non-invasive assessment of presence and distribution of hypoxia in
tumours. Nitroimidazoles are a class of electron affinic molecules that were shown to
accumulate in hypoxic cells in cultures and in vivo. [18F]-FMISO is the most frequently
employed tracer; its intracellular retention is dependent on oxygen concentration.
Consequently [18F]-FMISO has been used as a non-invasive technique for detection of hypoxia
in human. Different authors have demonstrated that it is suitable to localize and quantify
hypoxia. Thus, [18F]-FMISO PET has been studied to evaluate prognosis and predict treatment
response. However, some investigators report an unclear correlation between Eppendorf
measurements and standardized uptake values (SUV). This observation may be explained by the
structural complexity of hypoxic tumour tissues. Nevertheless, there is a need of
standardized procedures to acquire and quantify [18F]-FMISO uptake. Actually the use of this
tracer is very limited in clinic and the academic studies have included small populations of
patients and suffer of the heterogeneity of technical procedures.

The aim of this study is to determine the optimal acquisition protocol and treatment
parameters enable to describe [18F]-FMISO uptake in glioblastomas known to be hardly
influenced by hypoxia. Then, validate [18F]-FMISO-PET as a prognostic maker of recurrence.

We will introduce a pretherapy [18F]-FMISO PET-CT in the treatment planning of patients
suffering of different newly diagnosed glioblastoma and eligible to a radical treatment with
curative intent, consisting of conformational radiotherapy and chemotherapy. [18F]-FMISO
PET-CT results will not be take into account for the patient management. We will test
different acquisition protocols and use a wild panel of quantification parameters issued
from published studies and original ones developed by our team enable to describe
[18F]-FMISO uptake. Patients will be followed clinically and para-clinically during one year
after the end of the treatment according to the edited recommendations of each tumour type
and grade to analyze outcome (failure is define as persistent disease in the primary site,
progression of disease, locoregional relapse after complete response or distant metastasis).
Thus we will be able to measure failure free survival and determine overall survival.