Novel PET and Near Infrared Imaging Probes for the Specific Detection of Bacterial Infections Associated With Cardiac Devices
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Author + information
- Kiyoko Takemiya, MD, PhDa,
- Xinghai Ning, PhDb,
- Wonewoo Seo, PhDc,
- Xiaojian Wang, PhDb,
- Rafi Mohammad, PhDb,
- Giji Joseph, MSa,
- Jane S. Titterington, MD, PhDa,
- Colleen S. Kraft, MDd,
- Jonathan A. Nye, PhDc,
- Niren Murthy, PhDb,∗∗ (nmurthy{at}berkeley.edu),
- Mark M. Goodman, PhDc,∗∗∗ (mgoodma{at}emory.edu) and
- W. Robert Taylor, MD, PhDa,e,f,∗ (wtaylor{at}emory.edu)
- aEmory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, Georgia
- bUniversity of California at Berkeley, Department of Bioengineering, Berkeley, California
- cEmory University School of Medicine, Department of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Atlanta, Georgia
- dEmory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, Georgia
- eAtlanta Veterans Affairs Medical Center, Cardiology Division, Atlanta, Georgia
- fEmory University School of Medicine and Georgia Institute of Technology, Department of Biomedical Engineering, Atlanta, Georgia
- ↵∗Address for correspondence:
Dr. W. Robert Taylor, Department of Medicine, Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle, Suite 319 WMB, Atlanta, Georgia 30322. - ↵∗∗Dr. Niren Murthy, Department of Bioengineering, University of California Berkeley, 284 Hearst Memorial Mining Building, Berkeley, California 94720.
- ↵∗∗∗Dr. Mark Goodman, Center for Systems Imaging, Department of Radiology and Imaging Sciences, Emory University, 1841 Clifton Rd, NE, WWHC209, Atlanta, Georgia 30329.
Graphical abstract
Abstract
Objectives The aim of this study was to develop imaging agents to detect early stage infections in implantable cardiac devices.
Background Bacteria ingest maltodextrins through the specific maltodextrin transporter. We developed probes conjugated with either a fluorescent dye (maltohexaose fluorescent dye probe [MDP]) or a F-18 (F18 fluoromaltohexaose) and determined their usefulness in a model of infections associated with implanted cardiac devices.
Methods Stainless steel mock-ups of medical devices were implanted subcutaneously in rats. On post-operative day 4, animals were injected with either Staphylococcus aureus around the mock-ups to induce a relatively mild infection or oil of turpentine to induce noninfectious inflammation. Animals with a sterile implant were used as control subjects. On post-operative day 6, either the MDP or F18 fluoromaltohexaose was injected intravenously, and the animals were scanned with the appropriate imaging device. Additional positron emission tomography imaging studies were performed with F18-fluorodeoxyglucose as a comparison of the specificity of our probes (n = 5 to 9 per group).
Results The accumulation of the MDP in the infected rats was significantly increased at 1 h after injection when compared with the control and noninfectious inflammation groups (intensity ratio 1.54 ± 0.07 vs. 1.26 ± 0.04 and 1.20 ± 0.05, respectively; p < 0.05) and persisted for more than 24 h. In positron emission tomography imaging, both F18 fluoromaltohexaose and F18 fluorodeoxyglucose significantly accumulated in the infected area 30 min after the injection (maximum standard uptake value ratio 4.43 ± 0.30 and 4.87 ± 0.28, respectively). In control rats, there was no accumulation of imaging probes near the device. In the noninfectious inflammation rats, no significant accumulation was observed with F18 fluoromaltohexaose, but F18 fluorodeoxyglucose accumulated in the mock-up area (maximum standard uptake value 2.53 ± 0.39 vs. 4.74 ± 0.46, respectively; p < 0.05).
Conclusions Our results indicate that maltohexaose-based imaging probes are potentially useful for the specific and sensitive diagnosis of infections associated with implantable cardiac devices.
Footnotes
This work was supported by NIH 1R01EB020008, a generous gift from the John and Mary Brock Innovation Fund and Funding from the Georgia Research Alliance. Drs. Taylor, Goodman, Murthy, and Takemiya are listed as inventors of the maltodextrin imaging agents under a patent application held by Emory University and the Georgia Institute of Technology. Dr. Taylor has equity interest in Microbial Medical, Inc. Dr. Murthy owns equity in the Start-Up company that licensed the technology used in this article. Dr. Goodman is a co-founder of and has equity in Microbial Medical, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received August 29, 2016.
- Revision received February 4, 2018.
- Accepted February 8, 2018.
- 2019 American College of Cardiology Foundation
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