| Autor: |
Shah, Swati, Lai, Jianhao, Basuli, Falguni, Martinez-Orengo, Neysha, Patel, Reema, Turner, Mitchell L., Wang, Benjamin, Shi, Zhen-Dan, Sourabh, Suman, Peiravi, Morteza, Lyndaker, Anna, Liu, Sichen, Seyedmousavi, Seyedmojtaba, Williamson, Peter R., Swenson, Rolf E., Hammoud, Dima A. |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 8/14/2024, Vol. 16 Issue 760, p1-12, 12p |
| Abstrakt: |
The global incidence of invasive fungal infections (IFIs) has increased over the past few decades, mainly in immunocompromised patients, and is associated with high mortality and morbidity. Aspergillus fumigatus is one of the most common and deadliest IFI pathogens. Major hurdles to treating fungal infections remain the lack of rapid and definitive diagnosis, including the frequent need for invasive procedures to provide microbiological confirmation, and the lack of specificity of structural imaging methods. To develop an Aspergillus-specific positron emission tomography (PET) imaging agent, we focused on fungal-specific sugar metabolism. We radiolabeled cellobiose, a disaccharide known to be metabolized by Aspergillus species, and synthesized 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB) by enzymatic conversion of 2-deoxy-2-[18F]fluoroglucose ([18F]FDG) with a radiochemical yield of 60 to 70%, a radiochemical purity of >98%, and 1.5 hours of synthesis time. Two hours after [18F]FCB injection in A. fumigatus pneumonia as well as A. fumigatus, bacterial, and sterile inflammation myositis mouse models, retained radioactivity was only seen in foci with live A. fumigatus infection. In vitro testing confirmed production of β-glucosidase enzyme by A. fumigatus and not by bacteria, resulting in hydrolysis of [18F]FCB into glucose and [18F]FDG, the latter being retained by the live fungus. The parent molecule was otherwise promptly excreted through the kidneys, resulting in low background radioactivity and high target-to-nontarget ratios at A. fumigatus infectious sites. We conclude that [18F]FCB is a promising and clinically translatable Aspergillus-specific PET tracer. Editor's summary: Diagnosis of invasive Aspergillus infections can be difficult, in part because of lack of specificity of imaging methods. Here, Shah and colleagues rapidly synthesized an Aspergillus-specific 2-deoxy 2-[18F]fluorocellobiose ([18F]FCB) positron emission tomography (PET) tracer. Using mouse models of myositis and pulmonary infection, the authors showed that [18F]FCB injection resulted in retained radioactivity only at sites of live Aspergillus infection, but not at sites of heat-killed spore or bacterial injection, and that radioactivity on PET imaging localized to infiltrates and consolidations seen on coregistered CT scans. Longitudinal [18F]FCB PET/CT imaging of mice with Aspergillus myositis also detected infection progression and subclinical residual infection, highlighting the clinical potential of this Aspergillus-specific PET tracer. —Melissa L. Norton [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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