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

Early Phase 1

• Conditions: Glioma
• Interventions: Drug: 68Ga-BNOTA-PRGD2

• Registration Number: NCT01801371
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2013-02-22
• Study First Submitted QC: 2013-02-26
• Study First Posted: 2013-02-28
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-05
• Last Update Posted: 2017-04-07
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
68Ga-BNOTA-PRGD2	68Ga-BNOTA-PRGD2	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.

Primary Outcome Measures

Name	Time	Method
Semiquantitative measurement of standardized uptake values (SUVs) of lesions	1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China