Radionuclide Imaging of Fungal Infections and Correlation with the Host Defense Response

Abstract

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response’s metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. 18F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi.

Imaging of Invasive Fungal Infections- The Role of PET/CT

“…IFD frequently occurs in critically ill and immunocompromised patients, and the symptoms may be confounded by the patient's state. 31,32 The lung is the most common portal of entry of fungi into the human body. Inhaled fungal spores or mycelia are not efficiently eliminated by the immune system of patients with immunosuppression.…”

Radionuclide Imaging of Invasive Fungal Disease in Immunocompromised Hosts

“…In recent times, larger studies have reported the diagnostic utility of [ 18 F]FDG PET/CT in the initial evaluation and treatment response assessments of immunocompromised hosts with proven, probable, or possible IFD [26,91]. A recent study by Ankrah et al has provided insights into the relative lesion detection rates of [ 18 F]FDG PET/CT versus morphologic imaging with X-ray, CT, MRI, or ultrasound [92].…”

“…In addition to radiolabeled anti-fungal drugs targeting specific molecular structures of the fungi, other non-specific antimicrobial peptides have been explored for their possible application as noninvasive probes for IFD imaging [26,141]. Ubiquicidine 29-41 (UBI 29-41) radiolabeled with 99m Tc for SPECT or 68 Ga for PET imaging have been extensively used for pyogenic skeletal and soft tissue infections [142][143][144].…”

“…There is evidence showing a superior diagnostic performance for fluorine-18 fluorodeoxyglucose ([ 18 F]FDG) PET/CT over morphologic imaging with stand-alone CT in patients with IFD [24,25]. Novel radiopharmaceuticals targeting different metabolic pathways or molecular structures of pathogenic fungi are also in the pipeline for clinical translation [26]. In this review article, we aim to summarize the interplay of host immunity, immunodeficiency states, and the occurrence of IFD.…”

Special Issue: Host Defense against Fungi

“…A review by Ankrah at al. provides an overview of radionuclide imaging as an adjunct for diagnosis, as well as staging of dissemination and response to treatment in fungal infections, and includes a discussion of tracers at the preclinical stage [22]. Finally, a review of strategies to augment host defense through immunomodulatory approaches has been provided by Karavalakis and colleagues, with a focus on T-cell immunotherapy against invasive fungal disease in severely immunocompromised patients [23].…”