RGD PET/CT Imaging in COVID-19 Patients

Covid19 Clinical Trial

Official title:

[68Ga]Ga-DOTA-(RGD)2 PET/CT Imaging of Activated Endothelium in Lung Parenchyma of COVID-19 Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04596943
• Other study ID #: NL73551.091.20
• Secondary ID: 2020-001325-31
• Status: Completed
• Start date: October 15, 2020
• Est. completion date: March 1, 2021

Study information

• Verified date: March 2021
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Aim: We aim to evaluate αvβ3 integrin expression in proven COVID-19 infected patients with indicative findings on routine contrast-enhanced CT using [68Ga]Ga-DOTA-(RGD)2. If activated vascular endothelium in the lung parenchyma proceeds ARDS, as frequently observed during COVID-19 infection, imaging αvβ3 integrin expression using PET/CT could have potential as a clinical tool to characterize patients at early stages during disease and guide development of novel treatments targeting the vascular endothelium.

Study design: This is a prospective, observational non-randomized pilot study. Maximum 10 patients will undergo a [68Ga]Ga-DOTA-(RGD)2 PET/CT scan and CT-subtraction scan in the same procedure. 10-minutes/bed position static [68Ga]Ga-DOTA-(RGD)2 PET/CT scans of the thorax will be acquired starting at 60 minutes post injection.

Study population: Maximum 10 patients from the Infectious Diseases ward with proven COVID-19 infection and indicative pulmonary abnormalities on contrast-enhanced CT (CORADS 4-5) undergo PET/CT scans after injection of 70 μg (200 MBq) [68Ga]Ga-DOTA-(RGD)2 and CT-subtraction.

Intervention: All patients will undergo a [68Ga]Ga-DOTA-(RGD)2 PET/CT scan, and in the same procedure, a CT-subtraction scan.

Primary study objective: The primary objective of this study is to demonstrate and quantitate activation of the endothelium in the lung vasculature using [68Ga]Ga-DOTA-(RGD)2 PET/CT.

Secondary study objectives:

1. To assess the spatial correlation between [68Ga]Ga-DOTA-(RGD)2 uptake and abnormal findings on routine contrast-enhanced CT scan of the chest

2. To assess the spatial correlation between [68Ga]Ga-DOTA-(RGD)2 and CTS of the lung parenchyma

3. To assess the correlation between [68Ga]Ga-DOTA-(RGD)2 and laboratory results

4. To explore the correlation between [68Ga]Ga-DOTA-(RGD)2 uptake and clinical course of disease

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• a microbiologically proven SARS-CoV-19 infection

• pulmonary involvement as demonstrated on recent (<1 week) chest CT, classified as CORADS 4 or 5, with indicative findings such as ill-demarcated multifocal ground glass opacities, mixed ground glass and consolidations, predominant peripheral and basal distribution, vascular thickening, round shaped and/or (reversed) halo

• More than or equal to 18 years of age;

• Ability to provide written informed consent.

Exclusion Criteria:

• Contra-indication for PET: Pregnancy; Breast-feeding; Severe claustrophobia.

• Contra-indication for administration of iodine-containing contrast agents.

• Saturation <94% at room air (without need of additional oxygen)

• Previously documented lung abnormalities that can interfere with interpretation of research scans, e.g. extensive fibrosis, known interstitial lung disease, pulmonary metastases, known pulmonary involvement of granulomatous diseases.

• Oth Estimated creatinine clearance < 30mL/min according to the Cockcroft-Gault formula (or local institutional standard method) OR oligo-uric patients (<400mL/24hr)

Related Conditions & MeSH terms

• Covid19
• Endothelial Dysfunction
• PET Imaging

Intervention

Diagnostic Test:
• [68Ga]Ga-DOTA-(RGD)2 PET/CT
We have developed a dimeric cyclic RGD peptide conjugated with DOTA as a chelator. If labeled with the positron emitting radionuclide Gallium-68 (68Ga), [68Ga]Ga-DOTA-(RGD)2 can be used to visualize avß3 integrin expression with PET

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	uptake of [68Ga]Ga-DOTA-(RGD)2 in the lung parenchyma	The main study parameter is the uptake of [68Ga]Ga-DOTA-(RGD)2 in the lung parenchyma as quantified by PET/CT (SUVmean ±SD, SUVmax ±SD and SUVpeak ±SD).	2 months
Secondary	spatial correlation with chest-CT	spatial correlation (per lung segment) with ground-glass opacities, consolidation and vascular thickening	2 months
Secondary	spatial correlation with CT-subtraction	spatial correlation (per lung segment) with perfusion abnormalities as measured by CT-subtraction	2 months
Secondary	quantitative correlation with laboratory results	quantitative correlation with blood counts and differentiation, ferritin, D-dimer, CRP, liver enzyme panel (ALAT, ASAT, direct and indirect bilirubin, alkaline phosphatase, gamma-GT, LDH)	2 months
Secondary	explore correlation with clinical parameters	correlation with the following clinical parameters: (time to) eventual ICU admission, length of ICU stay (days), mechanical ventilation parameters, oxygen demand, total length of hospital stay (days)	2 months