Trial Information

Radiation Dosimetry, Plasma Pharmacokinetics, Biodistribution, Safety and Diagnostic Performance of 68Ga-BNOTA-PRGD2 in Healthy Volunteers and Lung Cancer Patients

Integrin αⅤβ3 is an important member of this 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 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). Among all the RGD
radiotracers studied, two PET imaging agents, 18F-Galacto-RGD and 18F-AH111585, have been
investigated in clinical trials, 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, 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, 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 are observed in animal
models to date.

For the further interests in clinical translation of 68Ga-BNOTA-PRGD2, a open-label dynamic
whole-body PET/CT study was designed to investigate radiation dosimetry, plasma
pharmacokinetics, biodistribution, safety and diagnostic performance of 68Ga-BNOTA-PRGD2 in
healthy volunteers and lung cancer patients. A single dose of nearly 111 MBq
68Ga-BNOTA-PRGD2 ( ≤ 40 µg BNOTA-PRGD2) will be intravenously injected into healthy
volunteers and lung cancer patients. Visual and semiquantitative method will be used to
assess the PET/CT images. Changes of blood pressure, pulse, respiration, temperature,
routine blood and urine tests, serum alanine aminotransferase, albumin, and creatinine, and
any adverse events will be collected from the volunteers. Adverse events will also be
observed in the patients.