Tc99m-annexin V-128 SPECT imaging of listeriosis in mice

1224 Objectives Ultrasound, CT, and MRI, currently the preferred imaging modalities to localize sites of infection, have low sensitivity and specificity in the setting of systemic bacterial disease. Here, we evaluate Tc99m annexin V-128, an in vivo marker of apoptosis, for SPECT imaging of disseminated bacterial infection, using a well-described mouse model that employs bioluminescent Listeria monocytogenes. Methods Mice were inoculated intravenously with bioluminescent Listeria, and in vivo bioluminescence imaging (BLI) was used to assess the location and extent of infection. Tc99m-annexin V-128 was then injected for SPECT imaging, and the two sets of images were correlated. Splenocytes of infected and uninfected mice were characterized for annexin binding by flow cytometry. In addition, treatment of the infection with ampicillin was imaged with BLI and Tc99m annexin V SPECT. Results Signals from BLI and Tc99m-annexin V-128 SPECT co-localized within the spleen and other organs. Decreases in Tc99m-annexin V-128 uptake and BLI signal within the spleen directly reflected the reduction of bacterial infection by ampicillin treatment [median spleen/median renal uptake of Tc99m-annexin V-128; low bacterial inoculum = 0.404 ± 0.053 (n = 7) vs. Rx = 0.225 ± 0.141 (n = 3), *p = 0.0153; high bacterial inoculum = 0.847 ± 0.301 (n = 5) vs. Rx = 0.291 ± 0.076 (n = 4), **p = 0.0093; control spleen = 0.104 ± 0.047 (n = 6)]. Autoradiography of spleens excised from the imaged mice revealed multifocal patterns of Tc99m-annexin V-128 uptake. Granulocytes and macrophages exhibiting IAF-annexin V-128 binding were increased in number in the infected spleen. In addition to the spleen, there were several other anatomic sites where a correlation between BLI and annexin V SPECT signals was observed. Conclusions Tc99m-annexin V-128 SPECT allowed for the detection and monitoring of disseminated bacterial infection and treatment in mice. Tc99m-annexin V-128 may be of use for the assessment of bacterial spread in sepsis or other disseminated bacterial infections. Research Support Gift funding from Atreus Pharmaceuticals/Ottawa Canada

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