Kiyoko Takemiya1, Xinghai Ning2, Wonewoo Seo3, Xiaojian Wang2, Rafi Mohammad2, Giji Joseph1, Jane S Titterington1, Colleen S Kraft4, Jonathan A Nye3, Niren Murthy5, Mark M Goodman6, W Robert Taylor7. 1. Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, Georgia. 2. University of California at Berkeley, Department of Bioengineering, Berkeley, California. 3. Emory University School of Medicine, Department of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Atlanta, Georgia. 4. Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, Georgia. 5. University of California at Berkeley, Department of Bioengineering, Berkeley, California. Electronic address: nmurthy@berkeley.edu. 6. Emory University School of Medicine, Department of Radiology and Imaging Sciences, Emory Center for Systems Imaging, Atlanta, Georgia. Electronic address: mgoodma@emory.edu. 7. Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, Georgia; Atlanta Veterans Affairs Medical Center, Cardiology Division, Atlanta, Georgia; Emory University School of Medicine and Georgia Institute of Technology, Department of Biomedical Engineering, Atlanta, Georgia. Electronic address: wtaylor@emory.edu.
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.
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.
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