Clinical trial NCT01940926: 68Ga-BNOTA-PRGD2 PET/CT in Patients With Rheumatoid Arthritis
Official title: Diagnostic Performance and Evaluation Efficacy of 68Ga-BNOTA-PRGD2 PET/CT in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
angiogenesis
68Ga-PRGD2
18F-FDG
positron emission tomography/computed tomography
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2013-09-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
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 positron emission tomography/computed tomography ( PET/CT) study to investigate the diagnostic performance and evaluation efficacy of 68Ga-BNOTA-PRGD2 in rheumatoid arthritis (RA) patients. A single dose of nearly 111 MBq 68Ga-BNOTA-PRGD2 (≤ 40 µg BNOTA-PRGD2) will be intravenously injected into patients with RA. Visual and semiquantitative method will be used to assess the PET/CT images. Whole body 18F-FDG PET/CT will be performed for comparison.

Detailed description: The Alpha(v)beta3 integrin, one of the most prominent members of integrin superfamily, is trans-membrane heterodimeric proteins which mediate cell-cell and cell-extracellular matrix adhesion. Integrin alpha(v)beta3 receptor plays an pivotal role in promoting, sustaining and regulating the angiogenesis and was identified as a marker of angiogenic vascular tissue. Cyclic arginine-glycine-aspartic acid (RGD) peptides was identified as a key integrin recognition motif which could strongly bind to integrin alpha(v)beta3 and inhibit new blood vessel formation. Animal study in antigen induced arthritis demonstrated that intra-articular administration of a cyclic RGD antagonist of alpha(v)beta3 leading to inhibition of cell infiltrate, synovial angiogenesis, pannus formation, cartilage erosions and even diminishing arthritis severity. For these properties, RGD peptide-based multimodality molecular probes have been developed for noninvasive imaging by targeting integrin alpha(v)beta3. And compared with 18F-FDG PET/CT, radiolabeled RGD imaging is a promising approach to visualize angiogenesis and provide a therapeutic target for anti-angiogenetic and anti-integrin therapy.

For the further interests in clinical translation of 68Ga-BNOTA-PRGD2, an open-label PET/CT study was designed to investigate the diagnostic performance and evaluation efficacy of 68Ga-BNOTA-PRGD2 in RA patients.

Eligibility criteria: Inclusion Criteria:

* Patients fulfilled the 1987 revised criteria of the American College of Rheumatology (ACR) for RA;
* Males and females, ≥18 years old

Exclusion Criteria:

* Concurrent medical conditions of other autoimmune diseases
* Latent or active joint infection or joint injury
* Renal dysfunction (serum level of creatinine more than 1.2 mg/dL)
* Females planning to bear a child recently or with childbearing potential
* Known severe allergy or hypersensitivity to intravenous 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

Primary outcomes:
measure: Semiquantitative assessment (Standardized Uptake Values = SUVs) of lesion
timeFrame: 1 year
Secondary outcomes:
measure: Number of participants with adverse events as a measure of safety
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Zhaohui Zhu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhu Z, Yin Y, Zheng K, Li F, Chen X, Zhang F, Zhang X. Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using (6)(8)Ga-PRGD2 PET/CT: a prospective proof-of-concept cohort study. Ann Rheum Dis. 2014 Jun;73(6):1269-72. doi: 10.1136/annrheumdis-2013-204820. Epub 2014 Feb 14.