Abstract

Invasive fungal disease (IFD) leads to increased mortality, morbidity, and costs of treatment in patients with immunosuppressive conditions. The definitive diagnosis of IFD relies on the isolation of the causative fungal agents through microscopy, culture, or nucleic acid testing in tissue samples obtained from the sites of the disease. Biopsy is not always feasible or safe to be undertaken in immunocompromised hosts at risk of IFD. Noninvasive diagnostic techniques are, therefore, needed for the diagnosis and treatment response assessment of IFD. The available techniques that identify fungal-specific antigens in biological samples for diagnosing IFD have variable sensitivity and specificity. They also have limited utility in response assessment. Imaging has, therefore, been applied for the noninvasive detection of IFD. Morphologic imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is the most applied technique. These techniques are neither sufficiently sensitive nor specific for the early diagnosis of IFD. Morphologic changes evaluated by CT and MRI occur later in the disease course and during recovery after successful treatment. These modalities may, therefore, not be ideal for early diagnosis and early response to therapy determination. Radionuclide imaging allows for targeting the host response to pathogenic fungi or specific structures of the pathogen itself. This makes radionuclide imaging techniques suitable for the early diagnosis and treatment response assessment of IFD. In this review, we aimed to discuss the interplay of host immunity, immunosuppression, and the occurrence of IFD. We also discuss the currently available radionuclide probes that have been evaluated in preclinical and clinical studies for their ability to detect IFD.

Highlights

  • pathogen recognition receptors (PRRs) participating in antifungal host immune activity belong to the Toll-like receptors (TLRs), C-type lectin receptors (CLRs), retinoic acid-inducible gene 1-like receptors (RLRs), and nucleotide-binding oligomerization domain-like receptors (NLRs) [41,42]

  • Several factors are prevailing in patients with hematological malignancies that are treated with Hematopoietic cell transplantation (HCT) that predispose to invasive fungal disease (IFD), including prior exposure to cytotoxic therapies, immunosuppressive therapy to prevent or treat graft-versus-host disease (GvHD), prior infection or colonization by pathogenic fungi, mucosal barrier disruption, and metabolic alterations [67,68]

  • It becomes imperative to distinguish between the progression of IFD versus co-existing non-fungal opportunistic infections or malignancies, especially in the context of new lesions appearing on followup [18 F]FDG positron-emission tomography (PET)/computed tomography (CT) in patients on antifungal therapy

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Summary

Introduction

Fungal infection may become disseminated, causing life-threatening invasive fungal disease (IFD). There are many factors that drive the burden of IFD seen in contemporary medical practice These factors include delayed recognition and diagnosis, the increasing rate of resistance to anti-fungal agents, and the increasing incidence of compromised host immunity as a side effect of medical therapies [4,5,6]. Radionuclide imaging techniques with positron-emission tomography (PET) or single-photon emission computed tomography (SPECT) target the pathogen that causes the disease or host immune response in infection imaging [22]. We will discuss the utility of radionuclide imaging techniques in diagnosing and managing IFD in the immunocompromised host using radiopharmaceuticals that target host immune response and the causative pathogen. Several fungal factors play prominent roles in driving the conversion of colonization to invasive disease, including fungal virulence factors and morphology (yeast versus hyphal form) [29,30]

Host Immunity against Invasive Fungal Disease
A schematic diagram
T-helper-17
Immunodeficiency States and Invasive Fungal Disease
Radionuclide Imaging of Invasive Fungal Disease
Targeting
Targeting Fungal Molecular Structure or Pathway
Targeting Fungal Iron Utilization
Targeting Fungal-Specific Molecular Structures
Targeting Hyphal-Specific Antigen
Targeting Fungal Cell Wall Chitin
Targeting Fungal Ribosomal RNA
Non-Specific Antimicrobial Peptides
Conclusions and Future Perspectives
Findings
68 Ga-ferrioxamine E for Aspergillus infection imaging
Full Text
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