Clinical trial NCT01527058: 68Ga-BNOTA-PRGD2 PET/CT in Healthy Volunteers and Lung Cancer Patients
Official title: Radiation Dosimetry, Plasma Pharmacokinetics, Biodistribution, Safety and Diagnostic Performance of 68Ga-BNOTA-PRGD2 in Healthy Volunteers and Lung Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Lung Cancer
Keywords: lung cancer
integrin receptor
68Ga-BNOTA-PRGD2
PET/CT
efficacy and safety
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2012-02-06
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is an open-label dynamic whole-body PET/CT (positron emission tomography/computed tomography) study for investigation of 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers:

  * Males and females, ≥30 and ≤ 70 years old
* Cancer patients:

  * Males and females, ≥30 years old
  * CT and/or 18F-FDG PET/CT diagnosis in suspicion of primary or recurrent lung cancer.
  * The lung cancer will be histologically confirmed or results of histology will be available.

Exclusion Criteria:

* 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 of lesions and biodistribution
timeFrame: One year
Secondary outcomes:
measure: Blood pressure
timeFrame: One year
measure: Pulse
timeFrame: One year
measure: Respiration frequency
timeFrame: One year
measure: Temperature
timeFrame: One year
measure: Routine blood test
timeFrame: One year
measure: Routine urine test
timeFrame: One year
measure: Serum alanine aminotransferase
timeFrame: One year
measure: Serum albumin
timeFrame: One year
measure: Serum creatinine
timeFrame: One year
measure: Adverse events collection
timeFrame: One year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Nuclear Medicine, Peking Union Medical College Hopital
Study officials:
affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science
name: Fang Li, MD
role: STUDY_CHAIR
References: