New pathogen-specific immunoPET/MR tracer for molecular imaging of a systemic bacterial infection
Quintanilla-Martinez de Fend, L
This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.7770.
The specific and rapid detection of Enterobacteriaceae, the most frequent cause of gram-negative bacterial infections in humans, remains a major challenge. We developed a non-invasive method to rapidly detect systemic Yersinia enterocolitica infections using immunoPET (antibody-targeted positron emission tomography) with [64Cu]NODAGA-labeled Yersinia-specific polyclonal antibodies targeting the outer membrane protein YadA. In contrast to the tracer [18F]FDG, [64Cu]NODAGA-YadA uptake co-localized in a dose dependent manner with bacterial lesions of Yersinia-infected mice, as detected by magnetic resonance (MR) imaging. This was accompanied by elevated uptake of [64Cu]NODAGA-YadA in infected tissues, in ex vivo biodistribution studies, whereas reduced uptake was observed following blocking with unlabeled anti-YadA antibody. We show, for the first time, a bacteria-specific, antibody-based, in vivo imaging method for the diagnosis of a Gram-negative enterobacterial infection as a proof of concept, which may provide new insights into pathogen-host interactions.
The research leading to these results has received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement n°602820, from the European Social Fund Baden-Württemberg (to SEA), and from the Deutsche Forschungsgemeinschaft (grant WI 3777/1-2; to SW).
Published online: February 26, 2016