Can Nuclear Imaging of Activated Macrophages with Folic Acid-Based Radiotracers Serve as a Prognostic Means to Identify COVID-19 Patients at Risk?

Cristina Müller,Britta Maurer,Roger Schibli

doi:10.3390/ph13090238

Abstract

Herein, we discuss the potential role of folic acid-based radiopharmaceuticals for macrophage imaging to support clinical decision-making in patients with COVID-19. Activated macrophages play an important role during coronavirus infections. Exuberant host responses, i.e., a cytokine storm with increase of macrophage-related cytokines, such as TNFα, IL-1β, and IL-6 can lead to life-threatening complications, such as acute respiratory distress syndrome (ARDS), which develops in approximately 20% of the patients. Diverse immune modulating therapies are currently being tested in clinical trials. In a preclinical proof-of-concept study in experimental interstitial lung disease, we showed the potential of 18F-AzaFol, an 18F-labeled folic acid-based radiotracer, as a specific novel imaging tool for the visualization and monitoring of macrophage-driven lung diseases. 18F-AzaFol binds to the folate receptor-beta (FRβ) that is expressed on activated macrophages involved in inflammatory conditions. In a recent multicenter cancer trial, 18F-AzaFol was successfully and safely applied (NCT03242993). It is supposed that the visualization of activated macrophage-related disease processes by folate radiotracer-based nuclear imaging can support clinical decision-making by identifying COVID-19 patients at risk of a severe disease progression with a potentially lethal outcome.

Highlights

Nuclear imaging, such as positron emission tomography (PET), has emerged as a valuable technique for the non-invasive diagnosis and monitoring of oncological and inflammatory diseases [1,2]
Among the variety of inflammatory cells, macrophages that are involved in numerous pathological processes in the context of cancer, autoimmune diseases and chronic inflammation, are interesting targets for imaging purposes
We propose the use of folate-based radiotracers as risk stratification tools to support clinical decision-making in patients with COVID-19 (Figure 1C)

Summary

Introduction

Nuclear imaging, such as positron emission tomography (PET), has emerged as a valuable technique for the non-invasive diagnosis and monitoring of oncological and inflammatory diseases [1,2]. ((BB)) AAnnaallooggyy ooff ddiisseeaasseepprrooggrreessssiioonn ininsesveevreerecacsaessesofoCf OCOVIVDID-1-91.9.(C(C))PProroppoosseeddccoonncceeppttooffuussiningg1818FF--AAzzaaFFooll--bbaasseedd ppoossiittrroonn eemmiissssiioonn tomography (PET) imaging for the diagnosis and monitoring of COVID-19 pneumonia and for monitoring the outcome and response to drugs targeting activated macrophages. SARS-CoV-2-infected innate immune cells including monocytes and macrophages and/or uninfected circulating cells recruited to the primary site of infection (e.g., airway epithelia or endothelial cells of multiple organs) can trigger massive immune reactions [25,26] This exuberant host response (cytokine storm with increase of, e.g., TNFα, IL-1β and IL-6 [25,27,28,29]), can lead to life-threatening complications, such as acute respiratory distress syndrome (ARDS), which develops in approximately 20% of patients and has a mortality rate of up to 60% [24]. Diverse immune modulating therapies are currently being evaluated for the treatment of COVID-19 patients in clinical trials [36]

Role of Chest Imaging in the Management of COVID-19 Patients

Folate-Based PET Radiotracers for Imaging of Activated Macrophages

Conclusions and Perspectives

Findings

Patents