Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging
| Autor: | Gerben M. Franssen, Caroline Hörtnagl, Cornelia Lass-Flörl, Clemens Decristoforo, Anna Helbok, Peter Laverman, Markus Schrettl, Hubertus Haas, Milos Petrik |
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| Rok vydání: | 2012 |
| Předmět: |
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 |
| Zdroj: | European Journal of Nuclear Medicine and Molecular Imaging, 39, 7, pp. 1175-83 European Journal of Nuclear Medicine and Molecular Imaging, 39, 1175-83 |
| ISSN: | 1619-7089 1619-7070 |
| DOI: | 10.1007/s00259-012-2110-3 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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