Abstract
Purpose
Here, we evaluate [99mTc]annexin V-128, an in vivo marker of apoptosis, for single photon emission computed tomography (SPECT) imaging of localization and antibiotic treatment of disseminated bacterial infection, using a well-described mouse model that employs bioluminescent Listeria monocytogenes.
Procedures
Sixteen groups of five mice in six separate experiments were infected with bioluminescent Listeria, and in vivo bioluminescence imaging (BLI) was performed each day, to assess the location and extent of infection and response to antibiotics. [99mTc]annexin V-128 was then injected for SPECT imaging, and the two sets of images were correlated and validated.
Results
Signals from BLI and [99mTc]annexin V-128 SPECT co-localized within the spleen and other organs including bone marrow, intestine, nasopharynx, and brain. Decreases in [99mTc]annexin V-128 uptake and BLI signal within the spleen directly reflected the reduction of bacterial infection by ampicillin treatment.
Conclusions
Tc-99m-Annexin V-128 uptake as observed by SPECT allowed for the detection of systemic listeriosis and ampicillin treatment in mice. [99mTc]annexin V-128 should be further explored for the assessment of bacterial spread and antibiotic efficacy in patients with disseminated bacterial infection.
Similar content being viewed by others
References
Vos FJ, Kullberg BJ, Sturm PD et al (2012) Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Medicine (Baltimore) 91:86–94
Depas G, Decortis T, Francotte N et al (2007) F-18 FDG PET in infectious diseases in children. Clin Nucl Med 32:593–598
Vos FJ, Bleeker-Rovers CP, Sturm PD et al (2010) 18F-FDG PET/CT for detection of metastatic infection in gram-positive bacteremia. J Nucl Med 51:1234–1240
Glaudemans AW, Galli F, Pacilio M et al (2013) Leukocyte and bacteria imaging in prosthetic joint infection. Eur Cell Mater 25:61–77
Vazquez-Boland JA, Kuhn M, Berche P et al (2001) Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 14:584–640
Palestro CJ, Love C, Bhargava KK (2009) Labeled leukocyte imaging: current status and future directions. Q J Nucl Med Mol Imaging 53:105–123
Britton KE, Wareham DW, Das SS et al (2002) Imaging bacterial infection with (99m)Tc-ciprofloxacin (Infecton). J Clin Pathol 55:817–823
Rusckowski M, Qu T, Pullman J et al (2000) Inflammation and infection imaging with a 99mTc-neutrophil elastase inhibitor in monkeys. J Nucl Med 41:363–374
Rennen HJ, Bleeker-Rovers CP, van Eerd JE et al (2004) 99mTc-labeled interleukin-8 for scintigraphic detection of pulmonary infections. Chest 126:1954–1961
Sarda L, Cremieux AC, Lebellec Y et al (2003) Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and sterile osteoarticular diseases. J Nucl Med 44:920–926
Penn DL, Kim C, Zhang K et al (2010) Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V. Nucl Med Biol 37:29–34
Rouzet F, Dominguez Hernandez M, Hervatin F et al (2008) Technetium 99m-labeled annexin V scintigraphy of platelet activation in vegetations of experimental endocarditis. Circulation 117:781–789
Blankenberg FG, Tait JF, Blankenberg TA et al (2001) Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V. Eur J Nucl Med 28:1384–1393
Tait JF, Smith C, Blankenberg FG (2005) Structural requirements for in vivo detection of cell death with 99mTc-annexin V. J Nucl Med 46:807–815
Hardy J, Kirkendoll B, Zhao H et al (2012) Infection of pregnant mice with Listeria monocytogenes induces fetal bradycardia. Pediatr Res 71:539–545
Hardy J, Margolis JJ, Contag CH (2006) Induced biliary excretion of Listeria monocytogenes. Infect Immun 74:1819–1827
Carrero JA, Unanue ER (2012) Mechanisms and immunological effects of apoptosis caused by Listeria monocytogenes. Adv Immunol 113:157–174
Bergmann S, Rohde M, Schughart K et al (2013) The bioluminescent Listeria monocytogenes strain Xen32 is defective in flagella expression and highly attenuated in orally infected BALB/cJ mice. Gut Pathog 5:19
Tsai YH, Disson O, Bierne H et al (2013) Murinization of internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses. PLoS Pathog 9:e1003381
Hardy J, Francis KP, DeBoer M et al (2004) Extracellular replication of Listeria monocytogenes in the murine gall bladder. Science 303:851–853
Tang XN, Wang Q, Koike MA et al (2007) Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia. J Nucl Med 48:1822–1828
Tait JF, Gibson D, Fujikawa K (1989) Phospholipid binding properties of human placental anticoagulant protein-I, a member of the lipocortin family. J Biol Chem 264:7944–7949
Tian R, Pan D (2012) Imaging myocardial ischemia and reperfusion injury via Cy5.5-annexin V. Nucl Med Mol Imaging 46:155–161
Hardy J, Chu P, Contag CH (2009) Foci of Listeria monocytogenes persist in the bone marrow. Dis Model Mech 2:39–46
Akers JC, Gonda D, Kim R et al (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113:1–11
Zhao H, Doyle TC, Coquoz O et al (2005) Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. J Biomed Opt 10:41210
Burns SM, Joh D, Francis KP et al (2001) Revealing the spatiotemporal patterns of bacterial infectious diseases using bioluminescent pathogens and whole body imaging. Contrib Microbiol 9:71–88
Sasser TA, Van Avermaete AE, White A et al (2013) Bacterial infection probes and imaging strategies in clinical nuclear medicine and preclinical molecular imaging. Curr Top Med Chem 13:479–487
Lorberboym M, Feldbrin Z, Hendel D et al (2009) The use of 99mTc-recombinant human annexin V imaging for differential diagnosis of aseptic loosening and low-grade infection in hip and knee prostheses. J Nucl Med 50:534–537
Carrero JA, Calderon B, Unanue ER (2004) Listeriolysin O from Listeria monocytogenes is a lymphocyte apoptogenic molecule. J Immunol 172:4866–4874
Acknowledgments
We gratefully acknowledge Pauline Chu for histology, Timothy Doyle and the SCI3 Facility at Stanford University for help with imaging, and Valeria Muzio for critical reading of the manuscript.
Conflict of Interest
We declare no potential conflict of interest with regard to this manuscript or the studies therein described. This work was funded in part by the Fund for Excellence in Pediatric Research from the Chambers Family Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hardy, J.W., Levashova, Z., Schmidt, T.L. et al. [99mTc]Annexin V-128 SPECT Monitoring of Splenic and Disseminated Listeriosis in Mice: a Model of Imaging Sepsis. Mol Imaging Biol 17, 345–354 (2015). https://doi.org/10.1007/s11307-014-0804-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11307-014-0804-6