Assessment of 18FLT PET-CT for Volume Definition of High-grade Gliomas (GLIO-TEP)

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT00624728

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

10.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

18F-Fluorothymidine is a recently developed PET tracer to image tumor cell proliferation. Very few data report an interest of using such a tracer for cerebral malignant tumor management. In our project, we want to compare the tumoral volumes obtained with PET and MRI, with the gold standard histopathological diagnosis according to the WHO grading malignancy scale and the Ki-67 proliferation index, for preoperative evaluation as much as for tumoral postoperative residue evaluation. Furthermore, we want to explore the interest of 18F-FLT-PET volume to better delineate tumoral volume in radiotherapeutic management of gliomas.

Condition or Disease	Intervention/Treatment	Phase
High-grade Glioma Astrocytoma Glioblastoma	Radiation: 18F Fluorothymidine PET CT	Phase 1/Phase 2

Detailed Description

Background: 18FDG is the most widely used tracer for oncologic positron emission tomography (PET). However, the high glucose utilization of normal gray matter limits its utility in brain explorations. More recently, 18FLT was introduced as a PET tracer for tumor imaging. It has been found useful for non-invasive assessment of the proliferation status of various tumors. Its potential clinical use in the evaluation of brain tumors has not been clearly determined because of sparse studies.
The primary objective of this study is to assess the positive predictive value of PET-CT uptake of 18FLT in diagnosing malignant tissue by comparison with the histopathological gold standard diagnosis according to the WHO grading malignancy scale and the Ki-67 proliferation index, at the time of preoperative evaluation.
Secondary objectives are: to describe and compare preoperative tumor volumes and postoperative residual tumor volumes as assessed by 18FLT PET-CT and MRI, and to describe a quantitative proliferation index with PET (SUV for "standardized uptake value").
Study design: This is an exploratory cross-sectional study at two separate times: pre-and postoperative. Eligible patients will be included consecutively. Histological samples will be analyzed blindly to imaging data. Assessments of PET-CT and MRI volumes will be blind to each other.
Procedure: After information and written informed consent and before surgery, patients will undergo MRI and 18F-FLT PET-CT to obtain the tumor volume according to both modalities. Then, surgeons will make different biopsies from i) areas with MR abnormalities and FLT uptake, ii) area with FLT uptake and no MR abnormality (on the surgery approach way or in not functional areas), iii) area with MR abnormality without any FLT uptake, iiii) area without any uptake where biopsy is possible because the area is on the surgery approach way. Then, the samples will be blindly analyzed to determine the Ki-67 proliferation index and WHO grading malignancy scale. Patients will undergo again 18F-FLT PET-TDM and MRI at least 4 weeks after surgery, in the week preceding radiotherapy, to determine residual tumor volumes.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Assessment of 18Fluoro-thymidine PET-CT for the Volume Definition of High-grade Gliomas (GLIO-TEP) : Correlation With Histopathology

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Nov 1, 2011

Actual Study Completion Date :

Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Radiation: 18F Fluorothymidine PET CT 18 FLT will be provided by the Laboratoire des Radiopharmaceutiques- Université Bordeaux2, Hôpital Xavier Arnozan and prepared according to the method described by Grierson and Shields ( Grierson J, Shields A. Nucl Med Biol 27 :143-156 ; 2000). Specific activity of 18FLT will be more than 37 GBq/µmol (>1Ci/µmol) corrected for decay at the end of bombardment of cyclotron target. Before tracer injection to patients, each dosis will be tested for pH and for radiochemical purity (> 95%) via HPLC technique and thin layer chromatography. 18FLT dosis will be injected intravenously to the patients (10 mL of salted isotonic solution with less than 10 % (v/v) of ethanol (USP). Administrated activity will be calculated estimating total body surface of patient (2,6 MBq/kg ou 0,07 mCi/kg) with maximal activity of 185 MBq. PET acquisition will be realized as follows : Dynamic acquisition in 3D mode for 35 min, Iterative reconstruction (OSEM) with and without attenuation correction.

Arm

Intervention/Treatment

Experimental: A

Radiation: 18F Fluorothymidine PET CT

18 FLT will be provided by the Laboratoire des Radiopharmaceutiques- Université Bordeaux2, Hôpital Xavier Arnozan and prepared according to the method described by Grierson and Shields ( Grierson J, Shields A. Nucl Med Biol 27 :143-156 ; 2000). Specific activity of 18FLT will be more than 37 GBq/µmol (>1Ci/µmol) corrected for decay at the end of bombardment of cyclotron target. Before tracer injection to patients, each dosis will be tested for pH and for radiochemical purity (> 95%) via HPLC technique and thin layer chromatography. 18FLT dosis will be injected intravenously to the patients (10 mL of salted isotonic solution with less than 10 % (v/v) of ethanol (USP). Administrated activity will be calculated estimating total body surface of patient (2,6 MBq/kg ou 0,07 mCi/kg) with maximal activity of 185 MBq. PET acquisition will be realized as follows : Dynamic acquisition in 3D mode for 35 min, Iterative reconstruction (OSEM) with and without attenuation correction.

Outcome Measures

Primary Outcome Measures

Predictive positive value of PET uptake for detection of malignant tissue (defined with Ki-67 proliferation index >15% in PET+ volumes) [before and during surgery]

Secondary Outcome Measures

Comparison of volumes defined by PET and MRI [before surgery and 4 weeks after surgery]
Description of a quantitative PET proliferation index ("standardized uptake value") [before surgery and 4 weeks after surgery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients over 18
suspicion of malignant glioma on MRI aspect
surgical indication with neuronavigation
signed informed consent
absence of contraindication for MRI
absence of pregnancy or breast-feeding

Exclusion Criteria:

women : pregnancy or breast-feeding or no oral or intra-uterine contraception (if not post-menopause)
secondary exclusion if high grade glioma diagnostic (glioblastoma or astrocytoma grade

is not confirmed after surgery with histopathology

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital St André, CHU de Bordeaux	Bordeaux		France	33000
2	Hôpital Pellegrin-tripode , CHU de Bordeaux	Bordeaux		France	33076

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Principal Investigator: Fernandez Philippe, Dr, University Hospital, Bordeaux, France
Study Chair: Perez Paul, Dr, University Hospital, Bordeaux, France