RGD PET/CT Imaging in COVID-19 Patients

Study Overview
=================
Brief 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: To assess the spatial correlation between [68Ga]Ga-DOTA-(RGD)2 uptake and abnormal findings on routine contrast-enhanced CT scan of the chest To assess the spatial correlation between [68Ga]Ga-DOTA-(RGD)2 and CTS of the lung parenchyma To assess the correlation between [68Ga]Ga-DOTA-(RGD)2 and laboratory results To explore the correlation between [68Ga]Ga-DOTA-(RGD)2 uptake and clinical course of disease

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

Conditions
-----------------
Covid19, Endothelial Dysfunction, PET Imaging

Intervention / Treatment
-----------------
* Diagnostic Test: [68Ga]Ga-DOTA-(RGD)2 PET/CT


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|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 αvβ3 integrin expression with PET|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, endothelial dysfunction, PET imaging, RGD-peptides