68Ga-BNOTA-PRGD2 PET/CT in Diagnosis and Evaluation of Glioma

Study Overview
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Brief Summary
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This is an open-label brain PET/CT (positron emission tomography/computed tomography) study to investigate the diagnostic performance and evaluation efficacy of 68Ga-BNOTA-PRGD2 in glioma patients. A single dose of nearly 111 MBq 68Ga-BNOTA-PRGD2 (≤40 µg BNOTA-PRGD2) will be intravenously injected into patients in suspicion of glioma. Visual and semiquantitative method will be used to assess the PET/CT images. Brain MRI with/without enhancement and 18F-FDG PET/CT will be performed for comparison. The postoperative pathology and integrin αvβ3 and CD34 immunohistochemical stains will also be used for correlation.

Detailed Description
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Integrin αvβ3 is an important member of integrin receptor family and expressed preferentially on various types of tumor cells and the activated endothelial cells of tumor angiogenesis, but not or very low on the quiescent vessel cells and other normal cells. Therefore, the integrin αvβ3 receptor is becoming a valuable target for diagnosis and response evaluation of malignant tumors. The tri-peptide sequence of arginine-glycine-aspartic acid (RGD) can specifically bind to the integrin αvβ3 receptor. Accordingly, a variety of radio-labeled RGD-based peptides have been developed for non-invasive imaging of integrin αvβ3 receptor expression via positron emission tomography (PET) or single photon emission computed tomography (SPECT). Among all RGD radiotracers, several PET imaging agents, including 18F-Galacto-RGD and 18F-AH111585, have been investigated in clinical trials for tumor diagnosis, and the results demonstrated that both radiotracers allowed the specific imaging of various types of tumors, and the tumor uptake correlated well with the expression of integrin αvβ3. Recently, serial RGD dimeric peptides with PEG linkers have been studied. The new types of RGD peptides showed much higher in vitro integrin αvβ3-binding affinity than the single RGD tri-peptide sequence, and importantly, they exhibited significantly increased tumor uptake and improved in vivo kinetics in animal models. As a representative, 68Ga-BNOTA-PRGD2 could be easily prepared and exhibited excellent in vivo behaviors in animal models. No adverse reactions have been observed in animal models to date. For the further interests in clinical translation of 68Ga-BNOTA-PRGD2, an open-label brain PET/CT study was designed to investigate the diagnostic performance and evaluation efficacy of 68Ga-BNOTA-PRGD2 in pre-surgery glioma patients.

Official Title
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Diagnostic Performance and Evaluation Efficacy of Brain 68Ga-BNOTA-PRGD2 PET/CT in Pre-surgery Glioma Patients

Conditions
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Glioma

Intervention / Treatment
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* Drug: 68Ga-BNOTA-PRGD2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, ≥18 years old； In suspicion of brain glioma on MRI； The tumor will be surgically removed and histological diagnosis will be available. Exclusion Criteria: Females planning to bear a child recently or with childbearing potential； Known severe allergy or hypersensitivity to IV radiographic contrast； Inability to lie still for the entire imaging time because of cough, pain, etc. Inability to complete the needed examinations due to severe claustrophobia, radiation phobia, etc. Concurrent severe and/or uncontrolled and/or unstable other medical disease that, in the opinion of the investigator, may significantly interfere with study compliance.

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: 68Ga-BNOTA-PRGD2<br>In patients in suspicion of glioma, single bolus of nearly 111 MBq 68Ga-BNOTA-PRGD2 will be intravenously injected 30 minutes before brain PET/CT to determine 68Ga-BNOTA-PRGD2 uptake in tumor and brain. | Drug: 68Ga-BNOTA-PRGD2<br>* Single intravenous bolus injection of nearly 111 MBq 68Ga-BNOTA-PRGD2 at 30 minutes before brain PET/CT scanning.<br>* Other names: 68Ga-p-SCN-Bn-NOTA-PEG3-RGD2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semiquantitative measurement of standardized uptake values (SUVs) of lesions | The semiquantitative analysis will be performed by the same person for all cases, and the standardized uptake value (SUV) of each tumor will be measured using a volume of interest (VOI) method. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety | Adverse events within 5 days after 68Ga-BNOTA-PRGD2 injection and PET/CT scanning will be collected and analyzed. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioma, Diagnostic imaging, Integrin receptor, 68Ga-BNOTA-PRGD2, PET/CT