Covid19, Endothelial Dysfunction, PET Imaging
Conditions
Keywords
COVID-19, endothelial dysfunction, PET imaging, RGD-peptides
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: 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
Interventions
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
Sponsors
Radboud University Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| uptake of [68Ga]Ga-DOTA-(RGD)2 in the lung parenchyma | 2 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| spatial correlation with chest-CT | 2 months | spatial correlation (per lung segment) with ground-glass opacities, consolidation and vascular thickening |
| spatial correlation with CT-subtraction | 2 months | spatial correlation (per lung segment) with perfusion abnormalities as measured by CT-subtraction |
| quantitative correlation with laboratory results | 2 months | 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) |
| explore correlation with clinical parameters | 2 months | 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) |
Countries
Netherlands
Outcome results
None listed