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
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
Other Name: RGD-PET/CT
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)
Radboudumc
Nijmegen, Netherlands