FAPI PET/CT to Detect Fibroblast Activity in Non-resolving ARDS

Of patients requiring mechanical ventilation in the ICU 23% meet criteria of the Acute Respiratory Distress Syndrome (ARDS). Mortality of this syndrome is high (35-46%) in moderate and severe ARDS. The fibroproliferative phase plays an important role in patients not recovering from ARDS. Bronchoalveolar lavage (BAL) can be used to investigate this process. However, quantitative assessment using BAL of fibroblast activity in both lungs is invasive, indirect and has yielded inconsistent results. This has precluded clinical utility. New methods to assess fibroblast activity in ARDS are therefore needed. A novel tool is PET/CT with the tracer \[68Ga\]-FAPI-46. \[68Ga\]-FAPI PET has the ability for reproducible and non-invasive measurement of fibroblast activity. Objective: 1. To relate pulmonary fibroblast activity in non-resolving ARDS, measured by FAPI-PET/CT, to 28 day mortality, ventilator-free days and alive at 28 days (VFD-28) and ICU length of stay. 2. To study the relationship between pulmonary fibroblast activity and systemic fibrotic and inflammatory biomarker. 3. To relate the pulmonary fibroblast activity on \[68Ga\]FAPI PET/CT with respiratory cell phenotypes and fibrotic and inflammatory mediators collected via bronchoalveolar lavage (BAL). Study design: This is a single center prospective observational feasibility study. We will include 20 ventilated patients with non-resolving ARDS. All mechanically ventilated patients in the ICU will be screened daily for ARDS. When ARDS is present for 5 consecutive days, patients will be included. Within 7 days after inclusion a \[68Ga\]FAPI-46 PET/CT scan will be performed. Within 48 hours of the PET/CT a broncho alveolar lavage and a nasal brush, will be performed. Blood will be drawn at inclusion and every 3rd day, as well as the day of the PET/CT. Daily registration of ventilatory and circulatory parameters, as well as clinical blood parameters, will be collected. End of study: The study will end when the patient has died, is discharged from the ICU or after 28 days.