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Karatay KB, Dogruoz Gungor N, Colak B, Biber Muftuler FZ, Aras O. Bacterial production of ciprofloxacin and potential usage as a radiotracer. PLoS One 2023; 18:e0291342. [PMID: 37943851 PMCID: PMC10635501 DOI: 10.1371/journal.pone.0291342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 08/29/2023] [Indexed: 11/12/2023] Open
Abstract
Infectious diseases caused by bacteria that have become resistant to antibiotics have increased in prevalence, necessitating new methods for their diagnosis and treatment. The aim of this study was to compare the efficacy of synthetic ciprofloxacin to that of organic ciprofloxacin produced by cave microorganisms, as well as to evaluate the feasibility of using organic ciprofloxacin radiolabeled with technetium-99m as an imaging agent. Organic ciprofloxacin produced by cave bacteria isolated from sediment taken from the dark zone of Antalya's "Yark Sinkhole," (Turkey's 14th deepest cave), was purified using high-performance liquid chromatography. Purified organic ciprofloxacin and standard ciprofloxacin were radiolabeled with technetium-99m (99mTc), and their uptake by pathogenic microorganisms as well as potential as an imaging agent were examined. According to thin-layer radiochromatography, radiolabeling efficiencies were 98.99 ± 0.34 (n = 7) and 91.25 ± 1.84 (n = 7) for radiolabeled organic ciprofloxacin and standard ciprofloxacin respectively. The binding efficiency of radiolabeled organic ciprofloxacin at the 240th minute was higher compared with radiolabeled standard ciprofloxacin, especially with P.aeruginosa, MRSA, VRE and E.coli. The results demonstrate that radiolabeling with 99mTc does not alter the biological behavior of organic ciprofloxacin, and radiolabeled organic ciprofloxacin has potential as an imaging agent for the detection of bacterial infection. The original value of the study is the monitoring of the antibiofilm effects of untouched cave-derived organic antibiotics by radiolabeling with a radionuclide.
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Affiliation(s)
- Kadriye Busra Karatay
- Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, Izmir, Turkey
| | - Nihal Dogruoz Gungor
- Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey
| | - Batu Colak
- Institute of Graduate Studies in Sciences, Istanbul University, Istanbul, Turkey
| | | | - Omer Aras
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
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Woong Yoo S, Young Kwon S, Kang SR, Min JJ. Molecular imaging approaches to facilitate bacteria-mediated cancer therapy. Adv Drug Deliv Rev 2022; 187:114366. [PMID: 35654213 DOI: 10.1016/j.addr.2022.114366] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 05/06/2022] [Accepted: 05/25/2022] [Indexed: 12/14/2022]
Abstract
Bacteria-mediated cancer therapy is a potential therapeutic strategy for cancer that has unique properties, including broad tumor-targeting ability, various administration routes, the flexibility of delivery, and facilitating the host's immune responses. The molecular imaging of bacteria-mediated cancer therapy allows the therapeutically injected bacteria to be visualized and confirms the accurate delivery of the therapeutic bacteria to the target lesion. Several hurdles make bacteria-specific imaging challenging, including the need to discriminate therapeutic bacterial infection from inflammation or other pathologic lesions. To realize the full potential of bacteria-specific imaging, it is necessary to develop bacteria-specific targets that can be associated with an imaging assay. This review describes the current status of bacterial imaging techniques together with the advantages and disadvantages of several imaging modalities. Also, we describe potential targets for bacterial-specific imaging and related applications.
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Affiliation(s)
- Su Woong Yoo
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeonnam, Korea
| | - Seong Young Kwon
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeonnam, Korea; Department of Nuclear Medicine, Chonnam National University Medical School, Hwasun, Jeonnam, Korea
| | - Sae-Ryung Kang
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeonnam, Korea
| | - Jung-Joon Min
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Jeonnam, Korea; Department of Nuclear Medicine, Chonnam National University Medical School, Hwasun, Jeonnam, Korea.
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3
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Signore A, Conserva M, Varani M, Galli F, Lauri C, Velikyan I, Roivainen A. PET imaging of bacteria. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00077-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Lopez‐Fernandez M, Jroundi F, Ruiz‐Fresneda MA, Merroun ML. Microbial interaction with and tolerance of radionuclides: underlying mechanisms and biotechnological applications. Microb Biotechnol 2021; 14:810-828. [PMID: 33615734 PMCID: PMC8085914 DOI: 10.1111/1751-7915.13718] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 11/09/2020] [Accepted: 11/12/2020] [Indexed: 11/26/2022] Open
Abstract
Radionuclides (RNs) generated by nuclear and civil industries are released in natural ecosystems and may have a hazardous impact on human health and the environment. RN-polluted environments harbour different microbial species that become highly tolerant of these elements through mechanisms including biosorption, biotransformation, biomineralization and intracellular accumulation. Such microbial-RN interaction processes hold biotechnological potential for the design of bioremediation strategies to deal with several contamination problems. This paper, with its multidisciplinary approach, provides a state-of-the-art review of most research endeavours aimed to elucidate how microbes deal with radionuclides and how they tolerate ionizing radiations. In addition, the most recent findings related to new biotechnological applications of microbes in the bioremediation of radionuclides and in the long-term disposal of nuclear wastes are described and discussed.
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Affiliation(s)
- Margarita Lopez‐Fernandez
- Department of MicrobiologyUniversity of GranadaAvenida Fuentenueva s/nGranada18071Spain
- Present address:
Institute of Resource EcologyHelmholtz‐Zentrum Dresden‐RossendorfBautzner Landstraße 400Dresden01328Germany
| | - Fadwa Jroundi
- Department of MicrobiologyUniversity of GranadaAvenida Fuentenueva s/nGranada18071Spain
| | - Miguel A. Ruiz‐Fresneda
- Department of MicrobiologyUniversity of GranadaAvenida Fuentenueva s/nGranada18071Spain
- Present address:
Departamento de Cristalografía y Biología EstructuralCentro Superior de Investigaciones Científicas (CSIC)Instituto de Química‐Física Rocasolano (IQFR)Calle Serrano 119Madrid28006Spain
| | - Mohamed L. Merroun
- Department of MicrobiologyUniversity of GranadaAvenida Fuentenueva s/nGranada18071Spain
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Silindir-Gunay M, Ozer AY. 99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents. J Drug Deliv Sci Technol 2020; 56:101571. [PMID: 32288835 PMCID: PMC7104933 DOI: 10.1016/j.jddst.2020.101571] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 01/01/2023]
Abstract
Easy and early detection of infection and inflammation is essential for early and effective treatment. In this study, PEGylated micelles were designed and both micelles and Levofloxacin were radiolabeled with 99mTcO4 - to develop potential radiotracers for detection of infection/inflammation. Radiolabeling efficiency, in vitro stability and bacterial binding of 99mTc-Levofloxacin and 99mTc-micelles were compared. The aim of this study is to formulate and compare 99mTc-Levofloxacin and 99mTc-micelles as infection and inflammation agents having different mechanisms for the accumulation at infection and inflammation site. PEGylated micelles were designed with a particle size of 80 ± 0.7 nm and proper characterization properties. High radiolabeling efficiency was achieved for 99mTc-Levofloxacin (96%) and 99mTc-micelles (87%). The radiolabeling efficiency was remained stable with some insignificant alterations for both radiotracers at 25 °C for 24 h. Although in vitro bacterial binding of 99mTc-levofloxacine was higher than 99mTc-micelles, 99mTc-micelles may also be evaluated potential agent due to long circulation and passive accumulation mechanisms at infection/inflammation site. Both radiopharmaceutical agents exhibit potential results in design, characterization, radiolabeling efficiency and in vitro bacterial binding point of view.
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Affiliation(s)
- Mine Silindir-Gunay
- Hacettepe University, Faculty of Pharmacy, Department of Radiopharmacy, 06100, Sıhhiye, Ankara, Turkey
| | - Asuman Yekta Ozer
- Hacettepe University, Faculty of Pharmacy, Department of Radiopharmacy, 06100, Sıhhiye, Ankara, Turkey
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Cho SY, Rowe SP, Jain SK, Schon LC, Yung RC, Nayfeh TA, Bingham CO, Foss CA, Nimmagadda S, Pomper MG. Evaluation of Musculoskeletal and Pulmonary Bacterial Infections With [ 124I]FIAU PET/CT. Mol Imaging 2020; 19:1536012120936876. [PMID: 32598214 PMCID: PMC7325456 DOI: 10.1177/1536012120936876] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 05/22/2020] [Accepted: 05/25/2020] [Indexed: 11/18/2022] Open
Abstract
PURPOSE Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine kinase inhibitor ([124I]FIAU) to image pulmonary and musculoskeletal infections. METHODS Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with [124I]FIAU PET/CT and 28 with [18F]FDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection. RESULTS Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of [124I]FIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for [18F]FDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively. CONCLUSIONS The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of [124I]FIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed.
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Affiliation(s)
- Steve Y. Cho
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Steven P. Rowe
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sanjay K. Jain
- Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lew C. Schon
- Department of Orthopedic Surgery, MedStar Union Memorial Hospital, Baltimore, MD, USA
- Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Rex C. Yung
- Division of Pulmonary Medicine and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Clifton O. Bingham
- Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Catherine A. Foss
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sridhar Nimmagadda
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Martin G. Pomper
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation. CONTRAST MEDIA & MOLECULAR IMAGING 2018. [PMID: 29531507 PMCID: PMC5817300 DOI: 10.1155/2018/9713691] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
During the last decade, the utilization of 68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of 68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management.
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Abstract
Diagnosis of deep-seated bacterial infection is difficult, as neither standard anatomical imaging nor radiolabeled, autologous leukocytes distinguish sterile inflammation from infection. Two recent imaging efforts are receiving attention: (1) radioactive derivatives of sorbitol show good specificity with Gram-negative bacterial infections, and (2) success in combining anatomical and functional imaging for cancer diagnosis has rekindled interest in 99mTc-fluoroquinolone-based imaging. With the latter, computed tomography (CT) would be combined with single-photon-emission-computed tomography (SPECT) to detect 99mTc-fluoroquinolone-bacterial interactions. The present minireview provides a framework for advancing fluoroquinolone-based imaging by identifying gaps in our understanding of the process. One issue is the reliance of 99mTc labeling on the reduction of sodium pertechnetate, which can lead to colloid formation and loss of specificity. Specificity problems may be reduced by altering the quinolone structure (for example, switching from ciprofloxacin to sitafloxacin). Another issue is the uncharacterized nature of 99mTc-ciprofloxacin binding to, or sequestration in, bacteria: specific interactions with DNA gyrase, an intracellular fluoroquinolone target, are unlikely. Labeling with 68Ga rather than 99mTc enables detection by positron emission tomography, but with similar biological uncertainties. Replacing the C6-F of the fluoroquinolone with 18F provides an alternative to pertechnetate and gallium that may lead to imaging based on drug interactions with gyrase. Gyrase-based imaging requires knowledge of fluoroquinolone action, which we update. We conclude that quinolone-based probes show promise for the diagnosis of infection, but improvements in specificity and sensitivity are needed. These improvements include the optimization of the quinolone structure; such chemistry efforts can be accelerated by refining microbiological assays.
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Affiliation(s)
- Syed Ali Raza Naqvi
- Department of Chemistry, Government College University, Faisalabad-38000, Pakistan
| | - Karl Drlica
- Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Science, Newark NJ USA
- Department of Microbiology, Biochemistry & Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Science, Newark, NJ USA
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Auletta S, Baldoni D, Varani M, Galli F, Hajar IA, Duatti A, Ferro-Flores G, Trampuz A, Signore A. Comparison of 99mTc-UBI 29-41, 99mTc-ciprofloxacin, 99mTc-ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF RADIOPHARMACEUTICAL CHEMISTRY AND BIOLOGY 2017; 63:37-47. [PMID: 28849632 DOI: 10.23736/s1824-4785.17.02975-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E. coli (ATCC 25922) and S. aureus (ATCC 43335). METHODS Stability controls were performed with the labelled radiopharmaceuticals during 6 hours in saline and serum. The in vitro binding to viable or killed bacteria was evaluated at 37 °C and 4 °C. For in vivo studies, Teflon cages were subcutaneously implanted in mice, followed by percutaneous infection. Biodistribution of i.v. injected radiolabelled radiopharmaceuticals were evaluated during 24 h in cages and dissected tissues. RESULTS Labelling efficiency of all radiopharmaceuticals ranged between 94% and 98%, with high stability both in saline and in human serum. In vitro binding assays displayed a rapid but poor bacterial binding for all tested agents. Similar binding kinetic occurred also with heat-killed and ethanol-killed bacteria. In the tissue cage model, infection was detected at different time points: 99mTc-UBI and 99mTcN-CiproCS2 showed higher infected cage/sterile cage ratio at 24 hours for both E. coli and S. aureus; 99mTc-Ciprofloxacin at 24 hours for both E. coli and at 4 hours for S. aureus; 111In-DTPA-biotin accumulates faster in both E. coli and S. aureus infected cages. CONCLUSIONS 99mTc-UBI, 99mTcN-CiproCS2 showed poor in vitro binding but good in vivo binding to E. coli only. 111In-DTPA-biotin showed poor in vitro binding but good in vivo binding to S. aureus and poor to E. coli. 99mTc-Ciprofloxacin showed poor in vitro binding but good in vivo binding to all tested bacteria. The mechanism of accumulation in infected sites remains to be elucidated.
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Affiliation(s)
- Sveva Auletta
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy
| | - Daniela Baldoni
- Infectious Diseases Research Laboratory, Department of Biomedicine, University Hospital, Basel, Switzerland
| | - Michela Varani
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy
| | - Filippo Galli
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy
| | - Iman A Hajar
- Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, Ferrara, Italy
| | - Adriano Duatti
- Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, Ferrara, Italy
| | - Guillermina Ferro-Flores
- Department of Radioactive Material, National Institute of Nuclear Investigations, Center of Nuclear Applications on Health, Ocoyoacac, Mexico
| | - Andrej Trampuz
- Unit of Septic Surgery, Center for Musculoskeletal Surgery, Charité, University of Medicine, Berlin, Germany
| | - Alberto Signore
- Unit of Nuclear Medicine, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy -
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van Oosten M, Hahn M, Crane LMA, Pleijhuis RG, Francis KP, van Dijl JM, van Dam GM. Targeted imaging of bacterial infections: advances, hurdles and hopes. FEMS Microbiol Rev 2015; 39:892-916. [PMID: 26109599 DOI: 10.1093/femsre/fuv029] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2015] [Indexed: 02/06/2023] Open
Abstract
Bacterial infections represent an increasing problem in modern health care, in particular due to ageing populations and accumulating bacterial resistance to antibiotics. Diagnosis is rarely straightforward and consequently treatment is often delayed or indefinite. Therefore, novel tools that can be clinically implemented are urgently needed to accurately and swiftly diagnose infections. Especially, the direct imaging of infections is an attractive option. The challenge of specifically imaging bacterial infections in vivo can be met by targeting bacteria with an imaging agent. Here we review the current status of targeted imaging of bacterial infections, and we discuss advantages and disadvantages of the different approaches. Indeed, significant progress has been made in this field and the clinical implementation of targeted imaging of bacterial infections seems highly feasible. This was recently highlighted by the use of so-called smart activatable probes and a fluorescently labelled derivative of the antibiotic vancomycin. A major challenge remains the selection of the best imaging probes, and we therefore present a set of target selection criteria for clinical implementation of targeted bacterial imaging. Altogether, we conclude that the spectrum of potential applications for targeted bacterial imaging is enormous, ranging from fundamental research on infectious diseases to diagnostic and therapeutic applications.
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Affiliation(s)
- Marleen van Oosten
- Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Markus Hahn
- Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Lucia M A Crane
- Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Rick G Pleijhuis
- Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
| | | | - Jan Maarten van Dijl
- Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
| | - Gooitzen M van Dam
- Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, the Netherlands
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11
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Inflammation. THE PATHOPHYSIOLOGIC BASIS OF NUCLEAR MEDICINE 2015. [PMCID: PMC7123337 DOI: 10.1007/978-3-319-06112-2_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Inflammation was described as early as 3000 BC in an Egyptian papyrus [1] and is still a common problem despite continuous advancements in prevention and treatment methods. The delineation of the site and extent of inflammation are crucial to the clinical management of infection and for monitoring the response to therapy [2].
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Lecina J, Cortés P, Llagostera M, Piera C, Suades J. New rhenium complexes with ciprofloxacin as useful models for understanding the properties of [99mTc]-ciprofloxacin radiopharmaceutical. Bioorg Med Chem 2014; 22:3262-9. [DOI: 10.1016/j.bmc.2014.04.058] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Accepted: 04/28/2014] [Indexed: 11/15/2022]
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Functional Imaging in Diagnostic of Orthopedic Implant-Associated Infections. Diagnostics (Basel) 2013; 3:356-71. [PMID: 26824928 PMCID: PMC4665528 DOI: 10.3390/diagnostics3040356] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Revised: 09/10/2013] [Accepted: 09/22/2013] [Indexed: 12/11/2022] Open
Abstract
Surgeries’ sterile conditions and perioperative antibiotic therapies decrease implant associated infections rates significantly. However, up to 10% of orthopedic devices still fail due to infections. An implant infection generates a high socio-economic burden. An early diagnosis of an infection would significantly improve patients’ outcomes. There are numerous clinical tests to diagnose infections. The “Gold Standard” is a microbiological culture, which requires an invasive sampling and lasts up to several weeks. None of the existing tests in clinics alone is sufficient for a conclusive diagnosis of an infection. Meanwhile, there are functional imaging modalities, which hold the promise of a non-invasive, quick, and specific infection diagnostic. This review focuses on orthopedic implant-associated infections, their pathogenicity, diagnosis and functional imaging.
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Wang JH, Sun GF, Zhang J, Shao CW, Zuo CJ, Hao J, Zheng JM, Feng XY. Infective severe acute pancreatitis: A comparison of 99mTc-ciprofloxacin scintigraphy and computed tomography. World J Gastroenterol 2013; 19:4897-4906. [PMID: 23946594 PMCID: PMC3740419 DOI: 10.3748/wjg.v19.i30.4897] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Revised: 04/12/2013] [Accepted: 05/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate 99mTc-ciprofloxacin scintigraphy compared with computed tomography (CT) for detecting secondary infections associated with severe acute pancreatitis (SAP) in swine.
METHODS: Six healthy swine were assigned to a normal control group (group A, n = 6). SAP was induced in group B (n = 9) and C (n = 18), followed by inoculation of the resulting pancreatic necroses with inactive Escherichia coli (E. coli) (group B) and active E. coli (group C), respectively. At 7 d after inoculation, a CT scan and a series of analyses using infecton imaging (at 0.5, 1, 2, 3, 4 and 6 h after the administration of 370 MBq of intravenous infecton) were performed. The scintigrams were visually evaluated and semi-quantitatively analyzed using region of interest assignments. The differences in infecton uptake and changes in the lesion-background radioactive count ratios (L/B) in the 3 groups were recorded and compared. After imaging detection, histopathology and bacterial examinations were performed, and infected SAP was regarded as positive. The imaging findings were compared with histopathological and bacteriological results.
RESULTS: In group A, 6 animals survived without infection in the pancreas. In group B, 7/9 swine survived and one suffered from infection. In group C, 15/18 animals survived with infection. Hence, the number of normal, non-infected and infected SAP swine was 6, 6 and 16, respectively. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the infecton method were 93.8% (15/16), 91.7% (11/12), 92.9% (26/28), 93.8% (15/16) and 91.7% (11/12), whereas these values for CT were 12.5% (2/16), 100.0% (12/12), 50.0% (14/28), 100.0% (2/2) and 46.2% (12/26), respectively. The changes in L/B for the infected SAP were significantly different from those of the non-infected and normal swine (P < 0.001). The mean L/B of the infectious foci at 0.5, 1, 2, 3, 4 and 6 h was 1.17 ± 0.10, 1.71 ± 0.30, 2.46 ± 0.45, 3.36 ± 0.33, 2.04 ± 0.37 and 1.1988 ± 0.09, respectively. At 3 h, the radioactive counts (2350.25 ± 602.35 k) and the mean L/B of the infectious foci were significantly higher than that at 0.5 h (P = 0.000), 1 h (P = 0.000), 2 h (P = 0.04), 4 h (P = 0.000) and 6 h (P = 0.000).
CONCLUSION: 99mTc-ciprofloxacin scintigraphy may be an effective procedure for detecting SAP secondary infections with higher sensitivity and accuracy than CT.
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Farouk N, El-Tawoosy M, Ayoub S, El-Bayoumy AS. Optimization of the reaction conditions for the preparation of 99mTc-celecoxib and its biological evaluation. J Radioanal Nucl Chem 2011. [DOI: 10.1007/s10967-011-1364-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Usefulness of 99mTc-ciprofloxacin scintigraphy in the diagnosis of prosthetic joint infections. Nucl Med Commun 2011; 32:44-51. [PMID: 20975609 DOI: 10.1097/mnm.0b013e328340e6fb] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the usefulness of 99Tc-ciprofloxacin scintigraphy (CFS) in patients with hip or knee arthroplasty and suspected infection. METHODS Forty patients (26 women, 14 men) with a mean age of 66±10 years and local pain in the hip (21), knee (16), or shoulder (three) prosthesis were recruited. CFS was performed at 1, 4, and 24 h after intravenous injection of 370 MBq. Anterior and posterior views centered on the affected joint were performed in all patients. A routine bone scan, 99Tc-hexamethylpropyleneamine oxime leukocyte scan, and 99Tc-colloid scan [leukocyte scintigraphy-bone marrow scintigraphy (LS-MS)] were performed. Final diagnosis of infection was confirmed by positive microbiological analysis or macroscopic evidence of purulent material. RESULTS Diagnosis of arthroplasty infection was established in 16 out 40 cases: coagulase-negative staphylococci (nine), Staphylococcus aureus (three), Enterococcus (one), and macroscopic infection in the remaining three cases. CFS imaging showed the 24-h image to be the best acquisition time-point. The sensitivity, specificity, negative predictive value, and positive predictive value for LS-MS were 75, 92, 86, and 85%, whereas for CFS at 24 h these figures were 88, 71, 67, and 89%. The sensitivity and specificity for LS-MS and for CFS at 24 h for hip were (74, 90, and 88, 85%) and for knee (83, 90 and 100, 50%). CONCLUSION CFS can be useful in the diagnosis of arthroplasty infection of the hip as a substitute for LS-MS. It is recommended that CFS images be obtained 24 h after injection. The lack of specificity of CFS makes this technique inadequate for knee prostheses in this series.
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A review on the clinical uses of SPECT/CT. Eur J Nucl Med Mol Imaging 2010; 37:1959-85. [PMID: 20182712 DOI: 10.1007/s00259-010-1390-8] [Citation(s) in RCA: 225] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Accepted: 01/11/2010] [Indexed: 01/02/2023]
Abstract
In the era when positron emission tomography (PET) seems to constitute the most advanced application of nuclear medicine imaging, still the conventional procedure of single photon emission computed tomography (SPECT) is far from being obsolete, especially if combined with computed tomography (CT). In fact, this dual modality imaging technique (SPECT/CT) lends itself to a wide variety of useful diagnostic applications whose clinical impact is in most instances already well established, while the evidence is growing for newer applications. The increasing availability of new hybrid SPECT/CT devices with advanced technology offers the opportunity to shorten acquisition time and to provide accurate attenuation correction and fusion imaging. In this review we analyse and discuss the capabilities of SPECT/CT for improving sensitivity and specificity in the imaging of both oncological and non-oncological diseases. The main advantages of SPECT/CT are represented by better attenuation correction, increased specificity, and accurate depiction of the localization of disease and of possible involvement of adjacent tissues. Endocrine and neuroendocrine tumours are accurately localized and characterized by SPECT/CT, as also are solitary pulmonary nodules and lung cancers, brain tumours, lymphoma, prostate cancer, malignant and benign bone lesions, and infection. Furthermore, hybrid SPECT/CT imaging is especially suited to support the increasing applications of minimally invasive surgery, as well as to precisely define the diagnostic and prognostic profile of cardiovascular patients. Finally, the applications of SPECT/CT to other clinical disorders or malignant tumours is currently under extensive investigation, with encouraging results in terms of diagnostic accuracy.
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