RGD PET/CT Imaging in COVID-19 Patients

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

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

Study Overview

• Status: Completed
• Conditions: Covid19; Endothelial Dysfunction; PET Imaging
• Intervention / Treatment: Diagnostic test: [68Ga]Ga-DOTA-(RGD)2 PET/CT

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500HB
    • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population for this pilot study exists of 10 evaluable patients with a proven SARS-CoV-19 infection and pulmonary involvement as demonstrated on chest CT, admitted to the Infectious Diseases ward. Patients presenting in the Radboud University Medical Center will be considered for recruitment, if they are over the age of 18.

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
spatial correlation with chest-CT	spatial correlation (per lung segment) with ground-glass opacities, consolidation and vascular thickening	2 months
spatial correlation with CT-subtraction	spatial correlation (per lung segment) with perfusion abnormalities as measured by CT-subtraction	2 months
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
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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: October 20, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: endothelial dysfunction; COVID-19; PET imaging; RGD-peptides
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: NL73551.091.20; 2020-001325-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No