The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma

Study Overview
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Brief Summary
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The epidermal growth factor receptor variant Ⅲ(EGFR vⅢ) is commonly detected in high-grade gliomas, which is also an important epitope in EGFR-targeted therapies and correlated to poor prognosis. However, detection of this mutant usually needs resected tumor samples. For biopsy samples, test results may not represent the EGFR vⅢ status of the whole tumor tissues because of the heterogeneity of tumor. It is also not applicable for patients who are not suitable for surgical procedure due to the tumor location or patients' general conditions. Because of the importance of the epidermal growth factor receptor (EGFR) signal pathway in oncogenesis, maintenance, and progression of high grade glioma, there has been an intense effort to develop noninvasive molecular imaging approach for the selection and monitoring of EGFR-targeted therapies. Based on investigators' previous study, investigators plan to perform PET scanning on the participants with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, investigators precisely obtain the tissue from thehot-spot on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be detected by molecular methods to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. Investigators' final goal is to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies.

Official Title
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The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma and Its Correlation to EGFRvIII

Conditions
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Glioma

Intervention / Treatment
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* Diagnostic Test: 89Zr-ABT806 PET


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical manifestations and imaging examination (CT, MRI, et al) are in accordance with high grade glioma No PET/CT scanning contraindications No MRI scanning contraindications Patients older than 18 years old ECOG score between 0 to 2 Patients with sufficient bone marrow, kidney and liver function reserve. All patients gave written informed consent. Exclusion Criteria: Patient who has received immune therapy, radiation therapy, chemotherapy, hormone drugs, biological products or other clinical trials within 14 days. Patient who has received EGFR monoclonal antibody therapy within 4 weeks. Patients who has not fully recovered form the past drug toxicity reaction (CTCAE in grade 2 or above). Patient who has received major surgery within 7 days. Patients with allergies to immunoglobulin. Breastfeeding women. pregnant women Patients with severe clinical condition. Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Grade Glioma<br>We plan to perform PET scanning on the patients with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806（1-2mCi）, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, we precisely obtained the tissue from thehot-spot on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status was detected by Sanger sequencing to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. The final goal was to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies. | Diagnostic Test: 89Zr-ABT806 PET<br>* Patients will be given IV bolus injection of 89Zr-ABT806(1-2mCi). The first 89Zr-ABT806 PET scan will be performed about 72 to 120 hours after injection of tracer. The second 89Zr-ABT806 PET scan will be performed about 120 to 168 hours after injection of tracer. Semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) and T/N ratio.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The sensitivity and specificity of 89Zr-ABT806 PET | After fusing the 89Zr-ABT806 PET and MRI images, investigators precisely obtained the tissue from thehot-spot on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be analyzed by molecular methods. The sensitivity and specificity of 89Zr-ABT806 PET will be measured with statistic methods. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall survival time of participants | regular follow-up | 4 years | 
| The progression-free survival time of participants | regular follow-up | 4 year | 
| The correlation between EGFRvIII mutation and prognosis of participants |  | 4 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioma, PET, EGFR vIII, Multimodal neuronavigation, Molecular pathology, PET-CT, Neuronavigation