Ga-67 Scan in Invasive Aspergillosis

Gómez, M. del Val; Gallardo, Fernando; Babé, J.G.; Cobo, J

doi:10.1097/00003072-200012000-00020

Cited by 2 publications

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“…Radiopharmaceuticals for which clinical applications have been proposed include 67 Ga-citrate [26], but it has known limitations in terms of pharmacokinetics, sensitivity and specificity, as it is a general marker for imaging malignancies and inflammatory processes. Even though 18 F-FDG has also recently been proposed as an imaging agent for IA [27], it has comparable limitations, in particular related to the low specificity for imaging glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

Petřík

Franssen

Haas

et al. 2012

Eur J Nucl Med Mol Imaging

108

114

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PurposeInvasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with 68Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising 68Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE).MethodsSiderophores were labelled with 68Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic μPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo.Results68Ga-siderophores were labelled with high radiochemical purity and specific activity. 68Ga-TAFC and 68Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, 68Ga-TAFC and 68Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by μPET with both compounds and increased with severity of the infection, correlating with abnormal CT images.Conclusion68Ga-TAFC and 68Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2110-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

Petřík

Franssen

Haas

et al. 2012

Eur J Nucl Med Mol Imaging

108

114

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“…It has emerged as an immensely powerful imaging technique in the field of oncology, but its use in infectious disease imaging is very much in its infancy ( Glaudemans et al, 2012 , 2015 ; Signore et al, 2015 ). Compared to SPECT of IPA using 67 Ga scintigraphy ( Tzen et al, 1999 ; Goméz et al, 2000 ), PET provides increased sensitivity and resolution through coincidence detection of photons emitted from radionuclei resulting from positron annihilation, with its success in oncology resulting from the use of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG), a diagnostic tracer that specifically accumulates in metabolically active inflammatory cells (neutrophils, macrophages, and lymphocytes), cancer cells, and during infectious processes ( Imperiale et al, 2010 ; Bassetti et al, 2017 ).…”

Section: Aspergillosis Imaging With [ 18 F]fdg Posmentioning

confidence: 99%

Molecular Imaging of Invasive Pulmonary Aspergillosis Using ImmunoPET/MRI: The Future Looks Bright

Thornton

2018

Front. Microbiol.

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Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immuno-compromised humans caused by the ubiquitous environmental mold Aspergillus. Biomarker tests for the disease lack sensitivity and specificity, and culture of the fungus from invasive lung biopsy is slow, insensitive, and undesirable in critically ill patients. A computed tomogram (CT) of the chest offers a simple non-intrusive diagnostic procedure for rapid decision making, and so is used in many hematology units to drive antifungal treatment. However, radiological indicators that raise the suspicion of IPA are either transient signs in the early stages of the disease or not specific for Aspergillus infection, with other angio-invasive molds or bacterial pathogens producing comparable radiological manifestations in a chest CT. Improvements to the specificity of radiographic imaging of IPA have been attempted by coupling CT and positron emission tomography (PET) with [18F]fluorodeoxyglucose ([18F]FDG), a marker of metabolic activity well suited to cancer imaging, but with limited use in invasive fungal disease diagnostics due to its inability to differentiate between infectious etiologies, cancer, and inflammation. Bioluminescence imaging using single genetically modified strains of Aspergillus fumigatus has enabled in vivo monitoring of IPA in animal models of disease. For in vivo detection of Aspergillus lung infections in humans, radiolabeled Aspergillus-specific monoclonal antibodies, and iron siderophores, hold enormous potential for clinical diagnosis. This review examines the different experimental technologies used to image IPA, and recent advances in state-of-the-art molecular imaging of IPA using antibody-guided PET/magnetic resonance imaging (immunoPET/MRI).

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Ga-67 Scan in Invasive Aspergillosis

Cited by 2 publications

References 2 publications

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

Molecular Imaging of Invasive Pulmonary Aspergillosis Using ImmunoPET/MRI: The Future Looks Bright

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