Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging
| العنوان: | Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging |
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| المؤلفون: | Gerben M. Franssen, Caroline Hörtnagl, Cornelia Lass-Flörl, Clemens Decristoforo, Anna Helbok, Peter Laverman, Markus Schrettl, Hubertus Haas, Milos Petrik |
| المصدر: | European Journal of Nuclear Medicine and Molecular Imaging, 39, 7, pp. 1175-83 European Journal of Nuclear Medicine and Molecular Imaging, 39, 1175-83 |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Siderophore, Pathology, medicine.medical_specialty, Siderophores, Gallium Radioisotopes, Hydroxamic Acids, Ferric Compounds, Peptides, Cyclic, Aspergillus fumigatus, Microbiology, Mice, 03 medical and health sciences, Pharmacokinetics, medicine, Animals, Tissue Distribution, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, biology, medicine.diagnostic_test, 030306 microbiology, business.industry, Translational research Immune Regulation [ONCOL 3], General Medicine, biology.organism_classification, In vitro, Rats, 3. Good health, Disease Models, Animal, Rats, Inbred Lew, Radiology Nuclear Medicine and imaging, Positron emission tomography, Positron-Emission Tomography, Renal physiology, Female, Specific activity, Pulmonary Aspergillosis, Radiopharmaceuticals, business, Ex vivo |
| الوصف: | Item does not contain fulltext PURPOSE: Invasive 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 (68)Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising (68)Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). METHODS: Siderophores were labelled with (68)Ga 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 muPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. RESULTS: (68)Ga-siderophores were labelled with high radiochemical purity and specific activity. (68)Ga-TAFC and (68)Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, (68)Ga-TAFC and (68)Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by muPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. CONCLUSION: (68)Ga-TAFC and (68)Ga-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. 01 juli 2012 |
| تدمد: | 1619-7089 1619-7070 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fce65ef9b37c49c23b7d546c097d891 https://doi.org/10.1007/s00259-012-2110-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8fce65ef9b37c49c23b7d546c097d891 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 16197089 16197070 |
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