99mTc-3PRGD2 SPECT/CT in Rheumatoid Arthritis Patients
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This is an open-label SPECT/CT (single photon emission computed tomography/computed
      tomography) study to investigate the diagnosis and efficacy evaluation performance of
      99mTc-3PRGD2 in rheumatoid arthritis patients. A single dose of nearly 11.1 MBq/kg body
      weight of 99mTc-3PRGD2 (≤20µg 3PRGD2) will be intravenously injected into the patients.
      Visual and semiquantitative method will be used to assess the whole-body planar and lesions
      section SPECT/CT images. Adverse events will also be observed in the patients.
    

Detailed description: 
      As a critical member of adhesion molecule integrin family and an important representative
      angiogenesis-related molecular, integrin αvβ3 is expressed at low levels on mature
      endothelial cells and normal cells, but it is overexpressed on the neovasculature endothelial
      cells, which has a high specificity and affinity in binding to the tri-peptide sequence of
      arginine-glycine-aspartic acid (RGD). Angiogenesis in the synovial membrane plays an
      important role in the pathogenesis of rheumatoid arthritis (RA). Therefore, radiolabeled RGD
      peptides can be used as molecular probe in radionuclide imaging to assess angiogenesis
      noninvasively in vitro and investigate the progress of RA, so as to achieve the goal of early
      diagnosis and efficacy evaluation for RA.

      Accordingly, a variety of radiolabeled RGD peptides have been used as radiotracers targeting
      the integrin αvβ3 expression to assess angiogenesis in vitro for noninvasive imaging via PET
      (positron emission tomography) or SPECT (single photon emission computed tomography). Some
      radiolabeled cyclic RGD peptides, such as 18F-Galacto-RGD, 18F-AH111585 and 99mTc-NC100692,
      have been investigated into clinical trials. 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 in both animal models and patients. Recently, several
      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, 99mTc-3PRGD2 could be easily prepared and
      exhibited excellent in vivo behaviors in animal models. No adverse reactions are observed in
      animal models to date.

      99mTc-3PRGD2, a novel tracer targeting integrin αvβ3 receptor, was tried to use in some
      tumors in recent years. However, there are few studies of 99mTc-3PRGD2 in other diseases
      except for tumors, especially no relevant reports in rheumatoid arthritis. Therefore, the
      investigators expect to further expand the applications of 99mTc-3PRGD2 in other diseases and
      to provide new methods and thoughts of assessing the efficacy of anti-αvβ3 or
      anti-angiogenesis therapy in rheumatoid arthritis. Based on the investigators previous animal
      study of 99mTc-3PRGD2 in RA, the investigators have strong interests in clinical trials of
      99mTc-3PRGD2. An open-label SPECT/CT study has been designed to investigate 99mTc-3PRGD2
      SPECT/CT in diagnosis and efficacy evaluation of RA. A single dose of nearly 11.1MBq/kg body
      weight 99mTc-3PRGD2 (≤20µg 3PRGD2) will be intravenously injected into the patients. Visual
      and semiquantitative method will be used to assess the whole-body planar and lesions section
      SPECT/CT images. Adverse events will also be observed in the patients.
    

Intervention name(s): 99mTc-3PRGD2
Intervention type(s): Drug
Intervention description(s): SPECT/CT scanning: single intravenous bolus injection of nearly 11.1 MBq/kg body weight of 99mTc-3PRGD2 on rheumatoid arthritis patients, whole-body planar and lesions section for determination the accumulation of 99mTc-3PRGD2 in the joints and other parts of the body.
For diagnosis study, each patient will be carried out SPECT/CT scanning once. For efficacy evaluation study, each patient will be carried out SPECT/CT scanning three times (before treatment, the midterm treatment and late stage treatment).
Other intervention name(s): 99mTc-HYNIC-3PRGD2
Intervention MeSH terms: HYNIC-3PRGD(2)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic