Safety and Diagnostic Performance of 99mTc-3PRGD2 SPECT/CT in Evaluation of Lung Cancer Patients
Integrin αvβ3 is an important member of integrin receptor family and expressed
preferentially on the activated endothelial cells of angiogenesis and some types of tumor
cells, 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 radiolabeled RGD-based peptides have
been developed for non-invasive imaging of integrin αvβ3 expression via single photon
emission computed tomography (SPECT)or positron emission tomography (PET). Among all the RGD
radiotracers studied, several RGD monomers have been investigated in clinical trials, and
the preliminary results demonstrated specific imaging of various types of tumors, and the
tumor uptake correlated well with the level of integrin αvβ3 expression. 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.
For the further interests in clinical translation of 99mTc-3PRGD2, an open-label SPECT/CT
study was designed to investigate the safety and diagnostic performance of 99mTc-3PRGD2 in
lung cancer patients. A single dose of nearly 11.1 MBq/kg body weight 99mTc-3PRGD2 ( ≤ 20 µg
3PRGD2) will be intravenously injected into the lung cancer patients. Visual and
semiquantitative method will be used to assess the whole-body planar and thoracic SPECT/CT
images. Adverse events will also be observed in the patients.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Visual and semiquantitative assessment of lesions and biodistribution
Visual analysis will be performed by consensus reading by at least 3 experienced nuclear medicine physician. The semiquantitative analysis will be performed by the same person for all the cases, and the tumor to background ratios(T/B) will be measured.
Fang Li, MD
Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science
China: National Natural Science Foundation