45
3.6 Applications of Fungal Siderophores
in Molecular Imaging
The low molecular weight chelators produced by fungi are referred to as siderophores and are key essential components to forage essential iron (Neilands 1995).
These attractive iron-chelating properties of siderophores make them an exclusive
system for fungal virulence and aid in diagnosis of fungal infections (Franceschini
et al. 2012; Leal et al. 2013).
Positron emission tomography (PET) is a kind of nuclear medicine imaging
method which is also used in the diagnosis of fungal aspergillosis to observe the
changes in various metabolic processes in the body of patients (Denning 1998).
To overcome the limitations and disadvantages of CT scan when diagnosing the
various fungal infections, fungal siderophores are widely used as imaging agents in
disease diagnosis and improved therapy. A. fumigatus produces a siderophore,
namely, triacetylfusarinine C (TAFC), for iron acquisition due to its application
toward the disease diagnosis. TAFC is considered to be a specific marker for invasive aspergillosis. TAFC is a main siderophore of the two important fungi such as
A. fumigatus and A. nidulans, while A. terreus and A. niger produce other siderophore types.
Recent researches showed that PET imaging can be done with the aid of siderophores for the diseases caused particularly by A. fumigatus. Aspergillosis in animal
models was detected by PET with the use of gallium-68 chelated by TAFC or bacterial siderophore ferrioxamine for selective accumulation in fungal cells. Thus,
TAFC acted as potential PET tracer with great sensitivity when it is labeled with the
radionuclide gallium-68 (68Ga). The two siderophores such as triacetylfusarinine
(TAFC) and ferrioxamine E (FOXE) were radiolabeled with 68Ga and used in PET
imaging of illness in rats caused by A. fumigatus (Petrik et al. 2010, 2012, 2014).
In a research study, an attempt has been made by coupling CT and PET with
[18F]-fluorodeoxyglucose ([18F]-FDG), an important marker of metabolic activity.
Though new diagnostic approach is developed, it showed limited advantages in the
invasive fungal disease diagnostics (Christopher 2018).
3.7 Conclusion
Aspergillus infections are emerging as life-threatening yet underappreciated and
underdeveloped as compared to other microbial infections. New strategies for
defense against Aspergillus infections are desperately needed to improve the survival rates of the patients with different forms of disease, and they are necessary to
develop new therapeutics and treatments. In this chapter, we discussed various
infections caused by Aspergillus species and their virulence in different stages of the
disease. The two major Aspergillus pathogens A. fumigatus and A. nidulans were
taken for the study, and their siderophoric system involved in biosynthetic pathway
3 Association of Fungal Siderophores in Human Diseases: Roles and Treatments
3.6 Applications of Fungal Siderophores
in Molecular Imaging
The low molecular weight chelators produced by fungi are referred to as siderophores and are key essential components to forage essential iron (Neilands 1995).
These attractive iron-chelating properties of siderophores make them an exclusive
system for fungal virulence and aid in diagnosis of fungal infections (Franceschini
et al. 2012; Leal et al. 2013).
Positron emission tomography (PET) is a kind of nuclear medicine imaging
method which is also used in the diagnosis of fungal aspergillosis to observe the
changes in various metabolic processes in the body of patients (Denning 1998).
To overcome the limitations and disadvantages of CT scan when diagnosing the
various fungal infections, fungal siderophores are widely used as imaging agents in
disease diagnosis and improved therapy. A. fumigatus produces a siderophore,
namely, triacetylfusarinine C (TAFC), for iron acquisition due to its application
toward the disease diagnosis. TAFC is considered to be a specific marker for invasive aspergillosis. TAFC is a main siderophore of the two important fungi such as
A. fumigatus and A. nidulans, while A. terreus and A. niger produce other siderophore types.
Recent researches showed that PET imaging can be done with the aid of siderophores for the diseases caused particularly by A. fumigatus. Aspergillosis in animal
models was detected by PET with the use of gallium-68 chelated by TAFC or bacterial siderophore ferrioxamine for selective accumulation in fungal cells. Thus,
TAFC acted as potential PET tracer with great sensitivity when it is labeled with the
radionuclide gallium-68 (68Ga). The two siderophores such as triacetylfusarinine
(TAFC) and ferrioxamine E (FOXE) were radiolabeled with 68Ga and used in PET
imaging of illness in rats caused by A. fumigatus (Petrik et al. 2010, 2012, 2014).
In a research study, an attempt has been made by coupling CT and PET with
[18F]-fluorodeoxyglucose ([18F]-FDG), an important marker of metabolic activity.
Though new diagnostic approach is developed, it showed limited advantages in the
invasive fungal disease diagnostics (Christopher 2018).
3.7 Conclusion
Aspergillus infections are emerging as life-threatening yet underappreciated and
underdeveloped as compared to other microbial infections. New strategies for
defense against Aspergillus infections are desperately needed to improve the survival rates of the patients with different forms of disease, and they are necessary to
develop new therapeutics and treatments. In this chapter, we discussed various
infections caused by Aspergillus species and their virulence in different stages of the
disease. The two major Aspergillus pathogens A. fumigatus and A. nidulans were
taken for the study, and their siderophoric system involved in biosynthetic pathway
3 Association of Fungal Siderophores in Human Diseases: Roles and Treatments