Catherine A Foss1,2, Liudmila Kulik3, Alvaro A Ordonez4, Sanjay K Jain4, V Michael Holers3, Joshua M Thurman3, Martin G Pomper5,4. 1. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 1550 Orleans St. CRB2 493, Baltimore, MD, 21228, USA. cfoss1@jhmi.edu. 2. Center for Infection and Inflammation Imaging Research, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, 21228, USA. cfoss1@jhmi.edu. 3. Department of Medicine, University of Colorado Denver, Aurora, CO, USA. 4. Center for Infection and Inflammation Imaging Research, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, 21228, USA. 5. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 1550 Orleans St. CRB2 493, Baltimore, MD, 21228, USA.
Abstract
PURPOSE: Diagnosis and therapeutic monitoring of chronic bacterial infection requires methods to detect and localize sites of infection accurately. Complement C3 activation fragments are generated and covalently bound to selective bacterial pathogens during the immune response and can serve as biomarkers of ongoing bacterial infection. We have developed several probes for detecting tissue-bound C3 deposits, including a monoclonal antibody (mAb 3d29) that recognizes the tissue-bound terminal processing fragments iC3b and C3d but does not recognize native circulating C3 or tissue-bound C3b. PROCEDURES: To determine whether mAb 3d29 could be used to detect chronic Mycobacterium tuberculosis infection non-invasively, aerosol-infected female C3HeB/FeJ mice were injected with [125I]3d29 mAb and either imaged using single-photon emission computed tomography (SPECT)/X-ray computed tomography (CT) imaging at 24 and 48 h after radiotracer injection or being subjected to biodistribution analysis. RESULTS: Discrete lesions were detected by SPECT/CT imaging in the lungs and spleens of infected mice, consistent with the location of granulomas in the infected animals as detected by CT. Low-level signal was seen in the spleens of uninfected mice and no signal was seen in the lungs of healthy mice. Immunofluorescence microscopy revealed that 3d29 in the lungs of infected mice co-localized with aggregates of macrophages (detected with anti-CD68 antibodies). 3d29 was detected in the cytoplasm of macrophages, consistent with the location of internalized M. tuberculosis. 3d29 was also present within alveolar epithelial cells, indicating that it detected M. tuberculosis phagocytosed by other CD68-positive cells. Healthy controls showed very little retention of fluorescent or radiolabeled antibody across tissues. Radiolabeled 3d29 compared with radiolabeled isotype control showed a 3.5:1 ratio of increased uptake in infected lungs, indicating specific uptake by 3d29. CONCLUSION: 3d29 can be used to detect and localize areas of infection with M. tuberculosis non-invasively by 24 h after radiotracer injection and with high contrast.
PURPOSE: Diagnosis and therapeutic monitoring of chronic bacterial infection requires methods to detect and localize sites of infection accurately. Complement C3 activation fragments are generated and covalently bound to selective bacterial pathogens during the immune response and can serve as biomarkers of ongoing bacterial infection. We have developed several probes for detecting tissue-bound C3 deposits, including a monoclonal antibody (mAb 3d29) that recognizes the tissue-bound terminal processing fragments iC3b and C3d but does not recognize native circulating C3 or tissue-bound C3b. PROCEDURES: To determine whether mAb 3d29 could be used to detect chronic Mycobacterium tuberculosisinfection non-invasively, aerosol-infected female C3HeB/FeJ mice were injected with [125I]3d29 mAb and either imaged using single-photon emission computed tomography (SPECT)/X-ray computed tomography (CT) imaging at 24 and 48 h after radiotracer injection or being subjected to biodistribution analysis. RESULTS: Discrete lesions were detected by SPECT/CT imaging in the lungs and spleens of infectedmice, consistent with the location of granulomas in the infected animals as detected by CT. Low-level signal was seen in the spleens of uninfected mice and no signal was seen in the lungs of healthy mice. Immunofluorescence microscopy revealed that 3d29 in the lungs of infectedmice co-localized with aggregates of macrophages (detected with anti-CD68 antibodies). 3d29 was detected in the cytoplasm of macrophages, consistent with the location of internalized M. tuberculosis. 3d29 was also present within alveolar epithelial cells, indicating that it detected M. tuberculosis phagocytosed by other CD68-positive cells. Healthy controls showed very little retention of fluorescent or radiolabeled antibody across tissues. Radiolabeled 3d29 compared with radiolabeled isotype control showed a 3.5:1 ratio of increased uptake in infected lungs, indicating specific uptake by 3d29. CONCLUSION: 3d29 can be used to detect and localize areas of infection with M. tuberculosis non-invasively by 24 h after radiotracer injection and with high contrast.
Authors: Stephanie L Davis; Eric L Nuermberger; Peter K Um; Camille Vidal; Bruno Jedynak; Martin G Pomper; William R Bishai; Sanjay K Jain Journal: Antimicrob Agents Chemother Date: 2009-09-08 Impact factor: 5.191
Authors: Allison M Murawski; Saumya Gurbani; Jamie S Harper; Mariah Klunk; Laurent Younes; Sanjay K Jain; Bruno M Jedynak Journal: J Nucl Med Date: 2014-07-31 Impact factor: 10.057
Authors: Gayatri Gowrishankar; Mohammad Namavari; Erwan Benjamin Jouannot; Aileen Hoehne; Robert Reeves; Jonathan Hardy; Sanjiv Sam Gambhir Journal: PLoS One Date: 2014-09-22 Impact factor: 3.240
Authors: Michelle H Larsen; Karen Lacourciere; Tina M Parker; Alison Kraigsley; Jacqueline M Achkar; Linda B Adams; Kathryn M Dupnik; Luanne Hall-Stoodley; Travis Hartman; Carly Kanipe; Sherry L Kurtz; Michele A Miller; Liliana C M Salvador; John S Spencer; Richard T Robinson Journal: Tuberculosis (Edinb) Date: 2020-02-11 Impact factor: 3.131
Authors: Paul Lecoq; Christian Morel; John O Prior; Dimitris Visvikis; Stefan Gundacker; Etiennette Auffray; Peter Križan; Rosana Martinez Turtos; Dominique Thers; Edoardo Charbon; Joao Varela; Christophe de La Taille; Angelo Rivetti; Dominique Breton; Jean-François Pratte; Johan Nuyts; Suleman Surti; Stefaan Vandenberghe; Paul Marsden; Katia Parodi; Jose Maria Benlloch; Mathieu Benoit Journal: Phys Med Biol Date: 2020-10-22 Impact factor: 3.609
Authors: Chao-Jen Wong; Leo Wang; V Michael Holers; Ashley Frazer-Abel; Silvère M van der Maarel; Rabi Tawil; Jeffrey M Statland; Stephen J Tapscott Journal: Hum Mol Genet Date: 2022-06-04 Impact factor: 5.121
Authors: Alvaro A Ordonez; Elizabeth W Tucker; Carolyn J Anderson; Claire L Carter; Shashank Ganatra; Deepak Kaushal; Igor Kramnik; Philana L Lin; Cressida A Madigan; Susana Mendez; Jianghong Rao; Rada M Savic; David M Tobin; Gerhard Walzl; Robert J Wilkinson; Karen A Lacourciere; Laura E Via; Sanjay K Jain Journal: J Clin Invest Date: 2021-03-01 Impact factor: 14.808
Authors: Yu Yan; Athira Narayan; Soonweng Cho; Zhiqiang Cheng; Jun O Liu; Heng Zhu; Guannan Wang; Bryan Wharram; Ala Lisok; Mary Brummet; Harumi Saeki; Tao Huang; Kathleen Gabrielson; Edward Gabrielson; Leslie Cope; Yasmine M Kanaan; Ali Afsari; Tammey Naab; Harris G Yfantis; Stefan Ambs; Martin G Pomper; Saraswati Sukumar; Vanessa F Merino Journal: Oncogene Date: 2021-08-02 Impact factor: 9.867