Clinical trial NCT01656785: 68Ga-BNOTA-PRGD2 PET/CT in Evaluation of Stroke
Official title: 68Ga-BNOTA-PRGD2 PET/CT in Evaluation of Angiogenesis Following Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Stroke
Keywords: stroke
cerebrovascular disease
angiogenesis imaging
68Ga-BNOTA-PRGD2
PET/CT
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2012-08-03
Enrollment: 50
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is an open-label brain PET/CT (positron emission tomography/computed tomography) study to investigate the diagnostic performance of 68Ga-BNOTA-PRGD2 in evaluation of stroke patients in convalescence. A single dose of nearly 111 MBq 68Ga-BNOTA-PRGD2 ( ≤ 40 µg BNOTA-PRGD2) will be intravenously injected into the patients. Visual and semi-quantitative method will be used to assess the PET/CT images. Changes of 18F-FDG PET/CT, enhanced brain MRI or CT, and any adverse events will be collected from the patients.

Detailed description: Integrin αvβ3 is an important member of this receptor family and expressed preferentially on regenerative vascular endothelial cells, but not or very low on the quiescent vessel cells and other normal cells. The αvβ3 integrin is a key mediator of angiogenesis and thus may be an important diagnostic and therapeutic target associated with cerebrovascular repair processes after stroke.

The tri-peptide sequence of arginine-glycine-aspartic acid (RGD) can specifically bind to the integrin αvβ3 receptor. Accordingly, a variety of radiolabeled RGD-based peptides have been developed for non-invasive imaging of integrin αvβ3 expression via positron emission tomography (PET) or single photon emission computed tomography (SPECT) to monitor the angiogenesis in clinical Oncology and Cardiology. In Neurology, angiogenesis imaging based on integrin αvβ3 receptor has not been found in clinical trials, but preclinical animal studies showed it had great potential for clinical translation. Recently, series of 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. As a representative, 68Ga-BNOTA-PRGD2 could be easily prepared and exhibited excellent in vivo behavior in animal models and also tumor or myocardial infarction patients. No adverse reactions are observed in animal models or patients to date.

For the further interests in clinical translation of 68Ga-BNOTA-PRGD2, an open-label brain PET/CT study was designed to investigate diagnostic performance of 68Ga-BNOTA-PRGD2 in stroke patients in convalescence. A single dose of nearly 111 MBq 68Ga-BNOTA-PRGD2 ( ≤ 40 µg BNOTA-PRGD2) will be intravenously injected into the patients. Visual and semiquantitative method will be used to assess the PET/CT images. Changes of brain 18F-FDG PET/CT, enhanced brain MRI or CT, and any adverse events will be collected from the patients.

Eligibility criteria: Inclusion Criteria:

stroke patients in convalescence:

* Males and females, ≥30 years old
* Confirmed cerebral infarction diagnosis
* With brain CT or MRI scans

Exclusion Criteria:

* Have cerebral tumors or other kinds of cerebral diseases
* Females planning to bear a child recently or with childbearing potential
* Renal function: serum creatinine \>3.0 mg/dL (270 μM/L)
* Liver function: any hepatic enzyme level more than 5 times upper limit of normal.
* Known severe allergy or hypersensitivity to IV radiographic contrast.
* Patients not able to enter the bore of the PET/CT scanner.
* 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.

Primary outcomes:
measure: Visual and semiquantitative assessment (Standardized Uptake Values = SUVs) of cerebral infarction region, SUV ratios (SUVinfarction/SUV contralateral)
timeFrame: 1 year
Secondary outcomes:
measure: Adverse events collection
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Nuclear Medicine, Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital
name: Zhaohui Zhu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: