99mTc-3PRGD2 SPECT/CT in Esophagus Cancer Patients

Safety and Diagnostic Performance of 99mTc-3PRGD2 SPECT/CT in Esophagus Cancer Patients

This is an open-label single photon emission computed tomography / computed tomography (SPECT/CT) study to investigate the safety and diagnostic performance of 99mTc-HYNIC-3PEG4-E[c(RGDfK)2) (99mTc-3PRGD2) in esophagus cancer patients. A single dose of nearly 11.1 MBq/kg body weight of 99mTc-3PRGD2 ( ≤ 20 µg 3PRGD2) will be intravenously injected into the patients in suspicion of esophagus cancer. Visual and semiquantitative method will be used to assess the whole-body planar and thoracic SPECT/CT images. Any adverse events will be collected from the patients.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: 99mTc-3PRGD2

Detailed Description

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 esophagus cancer patients. A single dose of nearly 11.1 MBq/kg body weight 99mTc-3PRGD2 ( ≤ 20 µg 3PRGD2) will be intravenously injected into the esophagus 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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350005
      • Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, ≥30 years old
• Thoracic CT and/or gastroscopy 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
• Known severe allergy or hypersensitivity to IV 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esophagus Cancer, 99mTc-3PRGD2, SPECT/CT; Determine if 99mTc-3PRGD2 SPECT/CT is safe and effective in diagnosis of Esophagus cancer patients.	Drug: 99mTc-3PRGD2; For patients in suspicion of esophagus cancer, single intravenous bolus injection of nearly 11.1 MBq/kg body weight of 99mTc-3PRGD2 on day one of the treatment period, whole-body planar and thoracic SPECT/CT to determine the accumulation of 99mTc-3PRGD2 in the tumors and the other parts of the body.; Other Names: 99mTc-HYNIC-3PRGD2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Assessment of Esophagus Lesions in 99mTc-3PRGD2 SPECT/CT Scan	Visual analysis will be performed by 3 experienced nuclear medicine physicians to observe the the uptake of 99mTc-3PRGD2 on esophagus lesions. The visual analysis interpreter's degree of suspicion for an abnormality was recorded with use of a 3-point with the following categories: score 1, no abnormal increased uptake; score 2, mildly increased uptake; score 3, definite focal increased uptake. The lesion was considered positive as malignancy if the lesion scored as 2 or higher.	one year
Semiquantitative Assessment of Esophagus Lesions in 99mTc-3PRGD2 SPECT/CT Scan	The semiquantitative analysis of the standardized uptake values (SUV) of 99mTc-3PRGD2 SPECT/CT was performed on esophagus lesion	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-FDG PET/CT Scan	18F-FDG PET/CT will be carried out in esophagus cancer patients to assess the uptake of esophagus lesions or distant metastasis and the standardized uptake values (SUVs) of these lesions will be measured.	one year
Laboratory Values	The blood level of CEA(carcino-embryonic antigen,ng/ml)in participants will be recorded.	one year
Adverse events collection	Adverse events within 5 days after the injection and scanning of the patients will be followed and assessed. The number of participants with adverse events and abnormal laboratory values will be recorded.	5 days
Contrast-enhanced CT	Contrast-enhanced CT will be carried out in esophagus cancer patients to observe the location and tumor diameter (cm).	one year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University
• Investigators: Study Director: Weibing Miao, MD, First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: April 16, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; HYNIC-3PRGD(2)
• Other Study ID Numbers: FirstAHFujian

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES