421 results on '"infection imaging"'
Search Results
2. Peptidoglycan-Targeted [18F]3,3,3-Trifluoro‑d‑alanine Tracer for Imaging Bacterial Infection
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Sorlin, Alexandre M, López-Álvarez, Marina, Biboy, Jacob, Gray, Joe, Rabbitt, Sarah J, Rahim, Junaid Ur, Lee, Sang Hee, Bobba, Kondapa Naidu, Blecha, Joseph, Parker, Mathew FL, Flavell, Robert R, Engel, Joanne, Ohliger, Michael, Vollmer, Waldemar, and Wilson, David M
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Chemical Sciences ,Biomedical Imaging ,Infectious Diseases ,Rare Diseases ,Lung ,2.2 Factors relating to the physical environment ,4.1 Discovery and preclinical testing of markers and technologies ,Infection ,infection imaging ,positron emission tomography ,peptidoglycan ,d-amino acids ,radiotracer ,metabolism ,Chemical sciences - Abstract
Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([111In]-WBC SPECT, [18F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall. We have previously reported the d-amino acid derived PET radiotracers d-methyl-[11C]-methionine, d-[3-11C]-alanine, and d-[3-11C]-alanine-d-alanine, which showed robust bacterial accumulation in vitro and in vivo. Given the clinical importance of radionuclide half-life, in the current study, we developed [18F]3,3,3-trifluoro-d-alanine (d-[18F]-CF3-ala), a fluorine-18 labeled tracer. We tested the hypothesis that d-[18F]-CF3-ala would be incorporated into bacterial peptidoglycan given its structural similarity to d-alanine itself. NMR analysis showed that the fluorine-19 parent amino acid d-[19F]-CF3-ala was stable in human and mouse serum. d-[19F]-CF3-ala was also a poor substrate for d-amino acid oxidase, the enzyme largely responsible for mammalian d-amino acid metabolism and a likely contributor to background signals using d-amino acid derived PET tracers. In addition, d-[19F]-CF3-ala showed robust incorporation into Escherichia coli peptidoglycan, as detected by HPLC/mass spectrometry. Based on these promising results, we developed a radiosynthesis of d-[18F]-CF3-ala via displacement of a bromo-precursor with [18F]fluoride followed by chiral stationary phase HPLC. Unexpectedly, the accumulation of d-[18F]-CF3-ala by bacteria in vitro was highest for Gram-negative pathogens in particular E. coli. In a murine model of acute bacterial infection, d-[18F]-CF3-ala could distinguish live from heat-killed E. coli, with low background signals. These results indicate the viability of [18F]-modified d-amino acids for infection imaging and indicate that improved specificity for bacterial metabolism can improve tracer performance.
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- 2024
3. Imaging the Bacterial Cell Wall Using N‑Acetyl Muramic Acid-Derived Positron Emission Tomography Radiotracers
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Lee, Sang Hee, Kim, Jung Min, López-Álvarez, Marina, Wang, Chao, Sorlin, Alexandre M, Bobba, Kondapa Naidu, Pichardo-González, Priamo A, Blecha, Joseph, Seo, Youngho, Flavell, Robert R, Engel, Joanne, Ohliger, Michael A, and Wilson, David M
- Subjects
Analytical Chemistry ,Engineering ,Electronics ,Sensors and Digital Hardware ,Chemical Sciences ,Infectious Diseases ,Bioengineering ,Biomedical Imaging ,Humans ,Muramic Acids ,Peptidoglycan ,Positron-Emission Tomography ,Fluorine Radioisotopes ,Bacteria ,Cell Wall ,infection imaging ,peptidoglycan ,N-acetyl muramic acid ,positron emission tomography ,fluorine-18 ,Biomedical Engineering ,Nanotechnology ,Analytical chemistry ,Electronics ,sensors and digital hardware - Abstract
Imaging infections in patients is challenging using conventional methods, motivating the development of positron emission tomography (PET) radiotracers targeting bacteria-specific metabolic pathways. Numerous techniques have focused on the bacterial cell wall, although peptidoglycan-targeted PET tracers have been generally limited to the short-lived carbon-11 radioisotope (t1/2 = 20.4 min). In this article, we developed and tested new tools for infection imaging using an amino sugar component of peptidoglycan, namely, derivatives of N-acetyl muramic acid (NAM) labeled with the longer-lived fluorine-18 (t1/2 = 109.6 min) radioisotope. Muramic acid was reacted directly with 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP) to afford the enantiomeric NAM derivatives (S)-[18F]FMA and (R)-[18F]FMA. Both diastereomers were easily isolated and showed robust accumulation by human pathogens in vitro and in vivo, including Staphylococcus aureus. These results form the basis for future clinical studies using fluorine-18-labeled NAM-derived PET radiotracers.
- Published
- 2023
4. Evaluating the Performance of Pathogen-Targeted Positron Emission Tomography Radiotracers in a Rat Model of Vertebral Discitis-Osteomyelitis
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Parker, Matthew FL, López-Álvarez, Marina, Alanizi, Aryn A, Luu, Justin M, Polvoy, Ilona, Sorlin, Alexandre M, Qin, Hecong, Lee, Sanghee, Rabbitt, Sarah J, Pichardo-González, Priamo A, Ordonez, Alvaro A, Blecha, Joseph, Rosenberg, Oren S, Flavell, Robert R, Engel, Joanne, Jain, Sanjay K, Ohliger, Michael A, and Wilson, David M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Bioengineering ,Emerging Infectious Diseases ,Infectious Diseases ,Biomedical Imaging ,4.1 Discovery and preclinical testing of markers and technologies ,Infection ,Humans ,Rats ,Animals ,Discitis ,4-Aminobenzoic Acid ,Escherichia coli ,Positron-Emission Tomography ,Staphylococcal Infections ,Osteomyelitis ,Bacteria ,Staphylococcus aureus ,Radiopharmaceuticals ,Infection imaging ,metabolism ,nuclear medicine ,S aureus ,positron emission tomography ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundVertebral discitis-osteomyelitis (VDO) is a devastating infection of the spine that is challenging to distinguish from noninfectious mimics using computed tomography and magnetic resonance imaging. We and others have developed novel metabolism-targeted positron emission tomography (PET) radiotracers for detecting living Staphylococcus aureus and other bacteria in vivo, but their head-to-head performance in a well-validated VDO animal model has not been reported.MethodsWe compared the performance of several PET radiotracers in a rat model of VDO. [11C]PABA and [18F]FDS were assessed for their ability to distinguish S aureus, the most common non-tuberculous pathogen VDO, from Escherichia coli.ResultsIn the rat S aureus VDO model, [11C]PABA could detect as few as 103 bacteria and exhibited the highest signal-to-background ratio, with a 20-fold increased signal in VDO compared to uninfected tissues. In a proof-of-concept experiment, detection of bacterial infection and discrimination between S aureus and E coli was possible using a combination of [11C]PABA and [18F]FDS.ConclusionsOur work reveals that several bacteria-targeted PET radiotracers had sufficient signal to background in a rat model of S aureus VDO to be potentially clinically useful. [11C]PABA was the most promising tracer investigated and warrants further investigation in human VDO.
- Published
- 2023
5. 18F-FDG PET CT in cardiac device infections - A Case series
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Awiral Saxena, Manjit Sarma, Bhagirath Bhad, Ramkesh Ratheesan, Padma Subramanyam, and P. Shanmuga Sundaram
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18-f fdg pet ct ,coronary stent infection ,prosthetic valve infection ,cied infection ,infection imaging ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Biology (General) ,QH301-705.5 - Abstract
With the increasing number of interventional cardiology procedures, the number of cardiac device infections (including pacemakers, prosthetic valves, coronary and aortic stents) have also increased. These infections can cause significant morbidity and can even lead to mortality if not managed promptly. If suspected clinically the first-line imaging modality is Trans-Thoracic Echocardiography, while Transesophageal Echocardiography is also used in selected cases. The confirmation of a cardiac device infection is mostly done with the help of blood or pus culture. Even though Echocardiography is a very efficient technique for the evaluation of the heart, it cannot differentiate infection from thrombus or fibrosis. With the increasing availability of Positron Emission Tomography CT (PET CT) machines worldwide, the use of 18F-FDG PET CT for infection imaging has gained traction, especially for cardiac device infection. Most of the recent studies show a good diagnostic accuracy of 18F-FDG PET CT with many of the recent diagnostic and management guidelines now acknowledging its role, especially in equivocal cases. We present six such cases where 18F-FDG PET CT provided valuable information either for diagnosis, confirming the presence of infection, delineating extent, therapy response or sometimes even helping appropriate treatment decision making in patients with suspected cardiac device infection.
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- 2024
- Full Text
- View/download PDF
6. A fluorogenic micrococcal nuclease-based probe for fast detection and optical imaging of Staphylococcus aureus in prosthetic joint and fracture-related infections.
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Schoenmakers, Jorrit W.A., López‑Álvarez, Marina, IJpma, Frank F.A., Wouthuyzen-Bakker, Marjan, McNamara 2nd, James O., van Oosten, Marleen, Jutte, Paul C., and van Dijl, Jan Maarten
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PROSTHESIS-related infections , *SYNOVIAL fluid , *STAPHYLOCOCCUS aureus infections , *JOINT infections , *NUCLEIC acid probes - Abstract
Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus. Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria. Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min. Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials. [ABSTRACT FROM AUTHOR]
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- 2024
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7. First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes.
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Kahts, Maryke, Summers, Beverley, Ndlela, Akhona Nkokheli, Gutta, Aadil, Nemutaduni, Phumudzo, More, Andrew, Parsoo, Aman, Ebenhan, Thomas, Zeevaart, Jan Rijn, Aras, Omer, and Sathekge, Mike Machaba
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LEUCOCYTES ,HEAVY metals ,SINGLE-photon emission computed tomography ,RADIOPHARMACEUTICALS ,RESEARCH funding ,CHELATING agents ,POSITRON emission tomography ,TERTIARY care ,DESCRIPTIVE statistics ,LONGITUDINAL method ,RESEARCH methodology ,COMPARATIVE studies ,RADIONUCLIDE imaging - Abstract
Introduction: Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([
99m Tc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89 Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89 Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of89 Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99m Tc]Tc-HMPAO-labelled leukocytes. Methods: Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99m Tc]Tc-HMPAO according to standardised methods, and [89 Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99m Tc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Results: Successful [89 Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89 Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99m Tc]Tc-HMPAOand [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99m Tc]Tc-HMPAOlabelled leukocytes outperformed [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89 Zr] Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Discussion: Although the [89 Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89 Zr]Zr-Df-Bz-NCS-labelled leukocytes. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
8. 18F-FDG PET CT in cardiac device infections - A Case series.
- Author
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Saxena, Awiral, Sarma, Manjit, Bhad, Bhagirath, Ratheesan, Ramkesh, Subramanyam, Padma, and Sundaram, P. Shanmuga
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POSITRON emission tomography computed tomography , *TRANSESOPHAGEAL echocardiography , *PATIENT decision making - Abstract
With the increasing number of interventional cardiology procedures, the number of cardiac device infections (including pacemakers, prosthetic valves, coronary and aortic stents) have also increased. These infections can cause significant morbidity and can even lead to mortality if not managed promptly. If suspected clinically the first-line imaging modality is Trans-Thoracic Echocardiography, while Transesophageal Echocardiography is also used in selected cases. The confirmation of a cardiac device infection is mostly done with the help of blood or pus culture. Even though Echocardiography is a very efficient technique for the evaluation of the heart, it cannot differentiate infection from thrombus or fibrosis. With the increasing availability of Positron Emission Tomography CT (PET CT) machines worldwide, the use of 18F-FDG PET CT for infection imaging has gained traction, especially for cardiac device infection. Most of the recent studies show a good diagnostic accuracy of 18F-FDG PET CT with many of the recent diagnostic and management guidelines now acknowledging its role, especially in equivocal cases. We present six such cases where 18F-FDG PET CT provided valuable information either for diagnosis, confirming the presence of infection, delineating extent, therapy response or sometimes even helping appropriate treatment decision making in patients with suspected cardiac device infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. 68Ga FAPI PET in a Renal Transplant Patient with Disseminated Nocardiosis–A Worthwhile Imaging Modality for Infection Imaging
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Kumar, Srinivas Ananth, Subramanian, Karthikeyan, Mittal, Bhagwant Rai, Singh, Harmandeep, Kumar, Rajender, and Singh, Sarbpreet
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- 2024
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10. Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections
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Jyotsna Bhatt Mitra, Saurav Chatterjee, Anuj Kumar, Elina Khatoon, Ashok Chandak, Sutapa Rakshit, Anupam Bandyopadhyay, and Archana Mukherjee
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Antimicrobial peptides ,Ubiquicidin ,Infection imaging ,68Ga radiopharmaceuticals ,Covalent probe ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background The urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting focal infections has yielded promising results. Augmenting the sensitivity of current PET and SPECT tracers could enable effective imaging of pathogenic bacteria, including drug-resistant strains.UBI (29–41), an antimicrobial peptide (AMP) fragment recognizes the S. aureus membrane through electrostatic binding. Radiolabeled UBI (29–41) is a promising SPECT and PET-based tracer for detecting focal infections. 2-APBA (2-acetyl-phenyl-boronic acid), a non-natural amino acid, specifically targets lysyl-phosphatidyl-glycerol (lysyl-PG) on the S. aureus membranes, particularly in AMP-resistant strains. We propose that combining UBI with 2-APBA could enhance the diagnostic potential of radiolabeled UBI. Results Present work aimed to compare the diagnostic potential of two radiolabeled peptides, namely UBI (29–41) and 2-APBA modified UBI (29–41), referred to as UBI and UBI-APBA. APBA modification imparted antibacterial activity to the initially non-bactericidal UBI against S. aureus by inducing a loss of membrane potential. The antibacterial activity demonstrated by UBI-APBA can be ascribed to the synergistic interaction of both UBI and UBI-APBA on the bacterial membrane. To enable PET imaging, we attached the chelator 1,4,7-triazacyclononane 1-glutaric acid 4,7-acetic acid (NODAGA) to the peptides for complexation with the positron emitter Gallium-68 (68Ga). Both NODAGA conjugates were radiolabeled with 68Ga with high radiochemical purity. The resultant 68Ga complexes were stable in phosphate-buffered saline and human serum. Uptake of these complexes was observed in S. aureus but not in mice splenocytes, indicating the selective nature of their interaction. Additionally, the APBA conjugate exhibited superior uptake in S. aureus while preserving the selectivity of the parent peptide. Furthermore, [68Ga]Ga-UBI-APBA demonstrated accumulation at the site of infection in rats, with an improved target-to-non-target ratio, as evidenced by ex-vivo biodistribution and PET imaging. Conclusions Our findings suggest that linking UBI, as well as AMPs in general, with APBA shows promise as a strategy to augment the theranostic potential of these molecules.
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- 2024
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11. Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections.
- Author
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Bhatt Mitra, Jyotsna, Chatterjee, Saurav, Kumar, Anuj, Khatoon, Elina, Chandak, Ashok, Rakshit, Sutapa, Bandyopadhyay, Anupam, and Mukherjee, Archana
- Subjects
SINGLE-photon emission computed tomography ,POSITRON emission tomography ,ANTIMICROBIAL peptides ,POLYETHYLENE terephthalate ,DRUG resistance in bacteria ,RADIOCHEMICAL purification - Abstract
Background: The urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting focal infections has yielded promising results. Augmenting the sensitivity of current PET and SPECT tracers could enable effective imaging of pathogenic bacteria, including drug-resistant strains.UBI (29–41), an antimicrobial peptide (AMP) fragment recognizes the S. aureus membrane through electrostatic binding. Radiolabeled UBI (29–41) is a promising SPECT and PET-based tracer for detecting focal infections. 2-APBA (2-acetyl-phenyl-boronic acid), a non-natural amino acid, specifically targets lysyl-phosphatidyl-glycerol (lysyl-PG) on the S. aureus membranes, particularly in AMP-resistant strains. We propose that combining UBI with 2-APBA could enhance the diagnostic potential of radiolabeled UBI. Results: Present work aimed to compare the diagnostic potential of two radiolabeled peptides, namely UBI (29–41) and 2-APBA modified UBI (29–41), referred to as UBI and UBI-APBA. APBA modification imparted antibacterial activity to the initially non-bactericidal UBI against S. aureus by inducing a loss of membrane potential. The antibacterial activity demonstrated by UBI-APBA can be ascribed to the synergistic interaction of both UBI and UBI-APBA on the bacterial membrane. To enable PET imaging, we attached the chelator 1,4,7-triazacyclononane 1-glutaric acid 4,7-acetic acid (NODAGA) to the peptides for complexation with the positron emitter Gallium-68 (
68 Ga). Both NODAGA conjugates were radiolabeled with68 Ga with high radiochemical purity. The resultant68 Ga complexes were stable in phosphate-buffered saline and human serum. Uptake of these complexes was observed in S. aureus but not in mice splenocytes, indicating the selective nature of their interaction. Additionally, the APBA conjugate exhibited superior uptake in S. aureus while preserving the selectivity of the parent peptide. Furthermore, [68 Ga]Ga-UBI-APBA demonstrated accumulation at the site of infection in rats, with an improved target-to-non-target ratio, as evidenced by ex-vivo biodistribution and PET imaging. Conclusions: Our findings suggest that linking UBI, as well as AMPs in general, with APBA shows promise as a strategy to augment the theranostic potential of these molecules. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
12. First-in-human infection imaging with 89Zr-labelled leukocytes and comparison of scan quality with [99mTc]Tc-HMPAO-labelled leukocytes
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Maryke Kahts, Beverley Summers, Akhona Nkokheli Ndlela, Aadil Gutta, Phumudzo Nemutaduni, Andrew More, Aman Parsoo, Thomas Ebenhan, Jan Rijn Zeevaart, Omer Aras, and Mike Machaba Sathekge
- Subjects
infection imaging ,inflammation ,[99mTc]Tc-HMPAO ,labelled leukocytes ,WBC scan ,zirconium-89 ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
IntroductionNuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes.MethodsLeukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients.ResultsSuccessful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAO- and [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAO-labelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel.DiscussionAlthough the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes.
- Published
- 2024
- Full Text
- View/download PDF
13. Soft X-ray Tomography Reveals HSV-1-Induced Remodeling of Human B Cells
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Chen, Jian-Hua, Vanslembrouck, Bieke, Ekman, Axel, Aho, Vesa, Larabell, Carolyn A, Le Gros, Mark A, Vihinen-Ranta, Maija, and Weinhardt, Venera
- Subjects
Microbiology ,Biological Sciences ,Infectious Diseases ,Bioengineering ,Sexually Transmitted Infections ,2.1 Biological and endogenous factors ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,Humans ,Herpesvirus 1 ,Human ,Tomography ,X-Ray ,Capsid ,X-ray tomography ,soft X-rays ,infection imaging ,HSV-1 ,cell mapping ,cryo imaging - Abstract
Upon infection, viruses hijack the cell machinery and remodel host cell structures to utilize them for viral proliferation. Since viruses are about a thousand times smaller than their host cells, imaging virus-host interactions at high spatial resolution is like looking for a needle in a haystack. Scouting gross cellular changes with fluorescent microscopy is only possible for well-established viruses, where fluorescent tagging is developed. Soft X-ray tomography (SXT) offers 3D imaging of entire cells without the need for chemical fixation or labeling. Here, we use full-rotation SXT to visualize entire human B cells infected by the herpes simplex virus 1 (HSV-1). We have mapped the temporospatial remodeling of cells during the infection and observed changes in cellular structures, such as the presence of cytoplasmic stress granules and multivesicular structures, formation of nuclear virus-induced dense bodies, and aggregates of capsids. Our results demonstrate the power of SXT imaging for scouting virus-induced changes in infected cells and understanding the orchestration of virus-host remodeling quantitatively.
- Published
- 2022
14. 89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations
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Maryke Kahts, Hua Guo, Harikrishna Kommidi, Yanping Yang, Haluk Burcak Sayman, Beverley Summers, Richard Ting, Jan Rijn Zeevaart, Mike Sathekge, and Omer Aras
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Cell trafficking ,Infection imaging ,Inflammation ,PET ,Zirconium-89 ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. Results The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30–60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced high-contrast murine PET images at 1 h–5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. Conclusions Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.
- Published
- 2023
- Full Text
- View/download PDF
15. Exploring the potential of radiolabeled duramycin as an infection imaging probe.
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Kumar, Anuj, Mitra, Jyotsna Bhatt, Khatoon, Elina, Pramanik, Aparna, Sharma, Rohit K., Chandak, Ashok, Rakshit, Sutapa, and Mukherjee, Archana
- Subjects
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SINGLE-photon emission computed tomography , *ESCHERICHIA coli , *ANTIMICROBIAL peptides , *RADIOCHEMICAL purification , *BACTERIAL cell walls - Abstract
The continuous pursuit of designing an ideal infection imaging agent is a crucial and ongoing endeavor in the field of biomedical research. Duramycin, an antimicrobial peptide exerts its antimicrobial action on bacteria by specific recognition of phosphatidylethanolamine (PE) moiety present on most bacterial membranes, particularly Escherichia coli (E. coli). E. coli membranes contain more than 60% PE. Therefore, duramycin is an attractive candidate for the formulation of probes for in situ visualization of E. coli driven focal infections. The aim of the present study is to develop 99mTc labeled duramycin as a single‐photon emission computed tomography (SPECT)‐based agent to image such infections. Duramycin was successfully conjugated with a bifunctional chelator, hydrazinonicotinamide (HYNIC). PE specificity of HYNIC‐duramycin was confirmed by a dye release assay on PE‐containing model membranes. Radiolabeling of HYNIC–duramycin with 99mTc was performed with consistently high radiochemical yield (>90%) and radiochemical purity (>90%). [99mTc]Tc‐HYNIC‐duramycin retained its specificity for E. coli, in vitro. SPECT and biodistribution studies showed that the tracer could specifically identify E. coli driven infection at 3 h post injection. While 99mTc‐labeled duramycin is employed for monitoring early response to cancer therapy and cardiotoxicity, the current studies have confirmed, for the first time, the potential of utilizing 99mTc labeled duramycin as an imaging agent for detecting bacteria. Its application in imaging PE‐positive bacteria represents a novel and promising advancement. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. 89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations.
- Author
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Kahts, Maryke, Guo, Hua, Kommidi, Harikrishna, Yang, Yanping, Sayman, Haluk Burcak, Summers, Beverley, Ting, Richard, Zeevaart, Jan Rijn, Sathekge, Mike, and Aras, Omer
- Subjects
POSITRON emission tomography ,CELL imaging ,LEUCOCYTES - Abstract
Background: The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (
89 Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. Results: The89 Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30–60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered89 Zr-labelled leukocytes produced high-contrast murine PET images at 1 h–5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously89 Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89 Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. Conclusions: Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies. [ABSTRACT FROM AUTHOR]- Published
- 2023
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17. Imaging of bacterial infection: Harnessing positron emission tomography and Cherenkov luminescence imaging with UBI‐derived octapeptide.
- Author
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Mitra, Jyotsna Bhatt, Mukherjee, Archana, Kumar, Anuj, Chandak, Ashok, Rakshit, Sutapa, Yadav, Hansa D., Pandey, Badri Narain, and Sarma, Haladhar Dev
- Subjects
- *
POSITRON emission tomography , *BACTERIAL diseases , *RADIOACTIVE tracers , *ANTIMICROBIAL peptides , *ANIMAL models of inflammation , *STAPHYLOCOCCUS aureus infections - Abstract
Noninvasive imaging techniques for the early detection of infections are in high demand. In this study, we present the development of an infection imaging agent consisting of the antimicrobial peptide fragment UBI (31–38) conjugated to the chelator 1,4,7‐triazacyclononane,1‐glutaric acid‐4,7‐acetic acid (NODAGA), which allows for labeling with the positron emitter Ga‐68. The preclinical evaluation of [68Ga]Ga–NODAGA–UBI (31–38) was conducted to investigate its potential for imaging bacterial infections caused by Staphylococcus aureus. The octapeptide derived from ubiquicidin, UBI (31–38), was synthesized and conjugated with the chelator NODAGA. The conjugate was then radiolabeled with Ga‐68. The radiolabeling process and the stability of the radio formulation were confirmed through chromatography. The study included both in vitro evaluations using S. aureus and in vivo evaluations in an animal model of infection and inflammation. Positron emission tomography (PET) and Cherenkov luminescence imaging (CLI) were performed to visualize the targeted localization of the radio formulation at the site of infection. Ex vivo biodistribution studies were carried out to quantify the uptake of the radio formulation in different organs and tissues. Additionally, the uptake of [18F]Fluorodeoxyglucose ([18F] FDG) in the animal model was also studied for comparison. The [68Ga]Ga–NODAGA–UBI (31–38) complex consistently exhibited high radiochemical purity (>90%) after formulation. The complex demonstrated stability in saline, phosphate‐buffered saline, and human serum for up to 3 h. Notably, the complex displayed significantly higher uptake in S. aureus, which was inhibited in the presence of unconjugated UBI (29–41) peptide, confirming the specificity of the formulation for bacterial membranes. Bacterial imaging capability was also observed in PET and CLI images. Biodistribution results indicated a substantial target‐to‐nontarget ratio of approximately 4 at 1 h postinjection of the radio formulation. Conversely, the uptake of [18F]FDG in the animal model did not allow for the discrimination of infected and inflamed sites. Our studies have demonstrated that [68Ga]Ga–NODAGA–UBI (31–38) holds promise as a radiotracer for imaging bacterial infections caused by S. aureus. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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18. Imaging-Selected Host Responses in the Context of Infections.
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Foss, Catherine A and Renslo, Adam R
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- *
INFECTION , *SOFT tissue injuries - Abstract
Recently developed molecular imaging approaches can be used to visualize specific host responses and pathology in a quest to image infections where few microbe-specific tracers have been developed and in recognition that host responses contribute to morbidity and mortality in their own right. Here we highlight several recent examples of these imaging approaches adapted for imaging infections. The early successes and new avenues described here encompass diverse imaging modalities and leverage diverse aspects of the host response to infection—including inflammation, tissue injury and healing, and key nutrients during host-pathogen interactions. Clearly, these approaches merit further preclinical and clinical study as they are complementary and orthogonal to the pathogen-focused imaging modalities currently under investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Imaging Techniques for Tuberculosis
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Teo, Tiffanie S. F., Kannivelu, Anbalagan, Srinivasan, Sivasubramanian, Peh, Wilfred C. G., Kauczor, Hans-Ulrich, Series Editor, Parizel, Paul M., Series Editor, Peh, Wilfred C. G., Series Editor, Brady, Luther W., Honorary Editor, Lu, Jiade J., Series Editor, and Ladeb, Mohamed Fethi, editor
- Published
- 2022
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20. Radiotracers for in situ infection imaging: Experimental considerations for in vitro microbial uptake of gallium-68-labeled siderophores.
- Author
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Akter, Asma, Cooper, Margaret S., Darwesh, Afnan M.F., Hider, Robert C., Blower, Philip J., Price, Nicholas M., Lyons, Oliver, Schelenz, Silke, Mehra, Varun, and Abbate, Vincenzo
- Subjects
- *
ESCHERICHIA coli , *SPECIES specificity , *ASPERGILLUS fumigatus , *POSITRON emission tomography , *CELL survival , *CANDIDA - Abstract
• Validation of in vitro 68Ga-siderophore uptake in E. coli and A. fumigatus. • Uptake results expressed as '% Added dose/109 CFU/mL' to compare bacterial and yeast species. • [68Ga]Ga-DFO-B uptake varies among microbial species. • [68Ga]Ga-DFO-B uptake has no significant effect on assessed bacterial and yeast cell viability. In vitro screening of gallium-68(68Ga)-siderophores in pathogens relevant to infections is valuable for determining species specificity, their effect on cell viability, and potential clinical applications. As the recognition and internalization of siderophores relies on the presence of receptor- and/or siderophore-binding proteins, the level of uptake can vary between species. Here, we report in vitro uptake validation in Escherichia coli with its native siderophore, enterobactin (ENT) ([68Ga]Ga-ENT), considering different experimental factors. Compared with other reporting methods of uptake, '% Added dose/109 CFU/mL (% AD/109 CFU/mL),' considering the total viable count, showed a better comparison among microbial species. Later, in vitro screening with [68Ga]Ga-desferrioxamine B (DFO-B) showed high uptake by Staphylococcus aureus and S. epidermidis ; moderate uptake by Pseudomonas aeruginosa ; poor uptake by E. coli, Candida albicans , and Aspergillus fumigatus ; and no uptake by Enterococcus faecalis and C. glabrata. Except for S. epidermidis , [68Ga]Ga-DFO-B did not reduce the cell viability. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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21. Preclinical evaluation of 2-[18F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection
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Lisanne M. Braams, Jürgen W.A. Sijbesma, Hendrikus H. Boersma, Jan Maarten van Dijl, Philip H. Elsinga, Andor W.J.M. Glaudemans, Riemer H.J.A. Slart, and Marleen van Oosten
- Subjects
Enterobacterales ,Gram-negative ,Sorbitol ,Infection imaging ,Clinical isolates ,Blood ,Microbiology ,QR1-502 ,Other systems of medicine ,RZ201-999 - Abstract
Fluorine-18-fluorodeoxyglucose ([18F]FDG) positron emission tomography (18F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology. The present study was aimed at exploring the potential of 2-[18F]-fluorodeoxysorbitol ([18F]FDS) as a tracer for detection of Enterobacterales infections. Sorbitol is a sugar alcohol that is commonly metabolized by bacteria of the Enterobacterales order, but not by mammalian cells, which makes it an attractive candidate for targeted bacterial imaging. The latter is important in view of the serious clinical implications of infections caused by Enterobacterales. Here we demonstrate that sorbitol-based PET can be applied to detect a broad range of clinical bacterial isolates not only in vitro, but also in blood and ascites samples from patients suffering from Enterobacterales infections. Notably, the possible application of [18F]FDS is not limited to Enterobacterales since Pseudomonas aeruginosa and Corynebacterium jeikeium also showed substantial uptake of this tracer. We conclude that [18F]FDS is a promising tracer for PET-imaging of infections caused by a group of bacteria that can cause serious invasive disease.
- Published
- 2023
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22. Leukocyte Labeling with Tc-99m-HMPAO: The Role of Leucocyte Numbers and Medication on the Labeling Efficacy and Image Quality.
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Karayel, Emre, Ocak, Meltem, and Tan, A. Seher Birteksöz
- Subjects
- *
LEUCOCYTES , *ERYTHROCYTES , *RADIOCHEMICAL purification , *LEUKOCYTE count , *BLOOD cells , *ANTICOAGULANTS , *MICROBIOLOGICAL synthesis - Abstract
Objectives: The aim of this study is to evaluation of Tc-99m-hexamethylpropyleneamineoxime (HMPAO)-labeled leukocytes in terms of radiochemical, biochemical, and microbiological quality controls and to examine the effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes, and imaging quality was evaluated. Methods: Thirty paients were included in our study who applied to Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Nuclear Medicine for Tc-99m-HMPAO-labeled leukocyte scintigraphy. Devices and chemicals used in the preparation of Tc-99m-HMPAO-labeled laukocytes were compared with other nuclear medicine clinics. Tc-99m-HMPAO-labeled leukocytes were evaluated in terms of radiochemical, biochemical, and microbiological quality controls. The effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes and imaging quality was evaluated. Results: The pH range of Tc-99m-HMPAO was 6-8 and the radiochemical purity was 90±2.04% (n=30), the radiochemical yield of Tc-99m- HMPAO-labeled leukocytes was 51±2.18% (n=30), the radiolabeling yield of Tc-99m-HMPAO-labeled leukocyte increased as the amount of white blood cell in the blood increased and whether the patients used any antibiotic, blood thinners, insulin and blood pressure medications did not affect the radiolabeling yield of Tc-99m-HMPAO-labeled leukocytes. The number of erythrocytes were removed at a rate of >99% in LPR by starch solution (6% HES; in the hemocytometric examination of Tc-99m-HMPAO-labeled leukocytes performed zeroth and 4th h, living/dead cell ratio was found 97.5% and the product was sterile. Conclusion: Tc-99m-HMPAO was labeled with leukocytes successfully, and Tc-99m-HMPAO-labeled leukocytes was safely injected to the patients as sterile without loss of vitality and aggregation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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23. PET and SPECT in the Evaluation of Cardiac Implantable Electronic Devices
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da Silva, Raphaella, Moreira, Renata, Mesquita, Cláudio Tinoco, editor, and Rezende, Maria Fernanda, editor
- Published
- 2021
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24. Radiosynthesis, quality control, biodistribution, and infection-imaging study of a new 99mTc-labeled ertapenem radiopharmaceutical
- Author
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Syed Ali Raza Naqvi, Tania Jabbar, Maha A. Alharbi, Asma Noureen, Nada K. Alharbi, Tauqir A. Sherazi, Anum Shahzadi, Ahmed Ezzat Ahmed, M. Shahzad Afzal, and M. Babar Imran
- Subjects
nuclear medicine ,metal complex ,infection imaging ,radiopharmaceuticals ,SPECT imaging ,ertapenem ,Chemistry ,QD1-999 - Abstract
Ertapenem is a member of carbapenem antibiotics used for the treatment of moderate-to-severe intra-abdominal, urinary tract, acute pelvic, and post-surgical gynecologic infections. The antibacterial activity of ertapenem is mediated through binding to penicillin-binding proteins which results in inhibiting the cross-linking of the peptidoglycan layer of the bacterial cell wall. Therefore, ertapenem can be labeled with technetium-99m (99mTc), a gamma emitter radionuclide, for the diagnosis of deep-seated bacterial infections, such as urinary tract, intra-abdominal, osteomyelitis, and post-surgical gynecologic infections. The labeling procedure was carried out by varying the reaction conditions, such as the amount of the ligand and reducing agent, pH, reaction time and temperature, and radioactivity. At optimized reaction conditions more than 93% 99mTc–ertapenem radioconjugate was obtained. 99mTc–ertapenem was found 90% intact in saline medium up to 6 h, while 88% intact in human blood serum up to 3 h. Biodistribution study showed target-to-non-target ratios of 2.91 ± 0.19, 2.39 ± 0.31, and 1.23 ± 0.22 in S. aureus, E. coli, and turpentine oil-infected rat models, respectively. The SPECT scintigraphy showed high uptake of 99mTc–ertapenem in bacterial-infected abscesses, and low counts were recorded in normal and turpentine oil-inflamed tissues. In conclusion, 99mTc–ertapenem can be a potent infection-imaging agent, which can diagnosis deep-seated bacterial infections at early stage but need further pre-clinical evaluation in variety of infection models.
- Published
- 2022
- Full Text
- View/download PDF
25. DIAGNOSTIC ACCURACY OF 99 MTC LABELLED UBIQUICIDIN (29-41) SPECT/CT FOR DIAGNOSIS OF OSTEOMYELITIS IN DIABETIC FOOT
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Muhammad Atif, Fida Hussain, Zaigham Salim Dar, Jameela Khatoon, Saadia Ajmal, and Muhammad Adil
- Subjects
diabetic foot ,infection imaging ,osteomyelitis ,99mtc-ubi (29-41) spect/ct ,Medicine ,Medicine (General) ,R5-920 - Abstract
Objective: To determine diagnostic accuracy of 99mTc labelled Ubiquicidin (29-41) SPECT/CT for detection of osteomyelitis in diabetic foot patients by taking bone biopsy as gold standard. Study Design: Cross-sectional validation study. Place and Duration of Study: Nuclear Medical Centre, Armed Forces Institute of Pathology, from Apr 2017 to Mar 2018. Methodology: Study assessed 122 patients of both genders, aged between 30-80 years (mean age=55.3 years), presenting with diabetic foot ulcers having suspicion of osteomyelitis, by 99mTc-Ubiquicidin (29-41) SPECT/CT followed by bone biopsy (histopathology and culture) taken as gold standard. Results: Among 122 patients [94 male (77%) and 28 female (23%)], osteomyelitis was histopathologically confirmed in 113 patients. 107 out of these patients were positive for osteomyelitis on 99mTc-UBI (29-41) SPECT/CT (true positives) while 6 were false negative. Out of 9 patients declared negative for osteomyelitis on histopathology and culture, 8 were negative on 99mTc-UBI (29-41) SPECT/CT as well (true negative) while only 1 case came out to be positive (false positive). Thus, the 99mTc-UBI (29-41) scan showed 94.6% sensitivity, 88.89% specificity, 99% positive predictive value, 57% negative predictive value with overall 94.2% diagnostic accuracy. Conclusion: 99mTc labelled Ubiquicidin (29-41) SPECT/CT scan can precisely localize infective focus, in diabetic foot osteomyelitis, with simultaneous discrimination between bone and soft tissues.
- Published
- 2021
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26. Novel Insights into Aspergillus fumigatus Pathogenesis and Host Response from State-of-the-Art Imaging of Host–Pathogen Interactions during Infection.
- Author
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Ortiz, Sébastien C., Pennington, Katie, Thomson, Darren D., and Bertuzzi, Margherita
- Subjects
- *
ASPERGILLUS fumigatus , *ASPERGILLOSIS , *MYCOSES , *DELAYED diagnosis , *PATHOGENESIS , *IMMUNITY , *INFECTION - Abstract
Aspergillus fumigatus spores initiate more than 3,000,000 chronic and 300,000 invasive diseases annually, worldwide. Depending on the immune status of the host, inhalation of these spores can lead to a broad spectrum of disease, including invasive aspergillosis, which carries a 50% mortality rate overall; however, this mortality rate increases substantially if the infection is caused by azole-resistant strains or diagnosis is delayed or missed. Increasing resistance to existing antifungal treatments is becoming a major concern; for example, resistance to azoles (the first-line available oral drug against Aspergillus species) has risen by 40% since 2006. Despite high morbidity and mortality, the lack of an in-depth understanding of A. fumigatus pathogenesis and host response has hampered the development of novel therapeutic strategies for the clinical management of fungal infections. Recent advances in sample preparation, infection models and imaging techniques applied in vivo have addressed important gaps in fungal research, whilst questioning existing paradigms. This review highlights the successes and further potential of these recent technologies in understanding the host–pathogen interactions that lead to aspergillosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
27. Validation of Radiosynthesis and First in-Human Dosimetry of 68 Ga-NOTA-UBI-29-41: A Proof of Concept Study.
- Author
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Thakral P, Rana N, Singh N, Das SS, Koley M, Gupta J, Malik D, and Sen I
- Abstract
Background: Antimicrobial peptides (AMPs) such as UBI-29-41 offer a distinctive approach for precise detection due to their unique interactions with bacteria and makes them promising candidates for specific and selective imaging. The study was aimed to corroborate the in-house manual synthesis of
68 Ga-NOTA-UBI-29-41, evaluate its uptake in patients with suspected infection, and estimate of patient-specific dosimetry to ensure optimal clinical application. Materials and Methods:68 Ga-NOTA-UBI-29-41 was synthesized by using a variable amount of UBI-29-41 (60-90 μg) to 555 MBq of Ga-68 in 0.05 M Hydrochloric acid (HCl) and heating the reaction sample for 12 min at 90°C at pH: 3.5-4 to obtain the radiopeptide with high yield and high radiochemical purity (RCP).68 Ga-NOTA-UBI-29-41 positron emission tomography/Computed tomography (CT) scans at variable timepoints were done to evaluate its biodistribution and maximum uptake time. Furthermore, patient-specific dosimetric estimation was done using the HERMES software. Results: A total of 5 μg/37 MBq (5 μg/mCi) of NOTA-UBI-29-41 for 12 min at 90°C were the optimal parameters to obtain 88%-90% of yield and 98%-99 % of RCP.68 Ga-NOTA-UBI-29-41 showed expeditious blood clearance and high renal excretion. The optimal time for imaging of infection with68 Ga-NOTA-UBI-29-41 was found to be at 60 min postinjection ( n = 8). The critical organ was the urinary bladder, receiving an average dose of 138.02 ± 45.92 µSv/MBq, followed by 53.81 ± 13.72 µSv/MBq for kidneys with a mean effective dose of 1.52 ± 0.64 mSv. Conclusion: The protocol for in-house manual labeling of68 Ga-NOTA-UBI-29-41 was reproducible, providing high yield and RCP.68 Ga-NOTA-UBI-29-41 administration was found to be safe and nontoxic. The favorable biodistribution and the first-in-human patient-specific dosimetry ensure optimal clinical application.- Published
- 2024
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28. Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives
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Ekaterina Dadachova and Drauzio E. N. Rangel
- Subjects
infection imaging ,antibiotics ,anti-fungals ,antimicrobial peptides ,antibodies ,HIV ,Medicine (General) ,R5-920 - Abstract
COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled anti-fungals for fungal infections imaging, radiolabeled pathogen-specific antibodies and molecular engineered constructs. In this opinion piece, we would like to discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections in order to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.
- Published
- 2022
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29. Evaluation of 68Ga-DOTA-Ubiquicidin (29-41) for imaging Staphylococcus aureus (Staph A) infection and turpentine-induced inflammation in a preclinical setting.
- Author
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BODDETI, DILIP KUMAR and KUMAR, VIJAY
- Subjects
- *
STAPHYLOCOCCUS aureus , *ANIMAL models of inflammation , *POSITRON emission tomography , *HINDLIMB , *INFLAMMATION - Abstract
Synthetic antimicrobial peptide fragment, 99mTc-Ubiquicidin 29-41, is shown to be sensitive and also specific for imaging bacterial infections. We undertook this study to explore the advantage of using a positron emission agent, 68Ga-DOTA-Ubiquicidin 29-41 (68Ga-DOTA-UBI), for detecting Staph-A infection in an animal model, and also evaluated its ability to distinguish a turpentine-induced sterile inflammation in an animal model. Pure Ga-68 was freshly eluted from a 68Ge/68Ga generator (IGG-100). DOTA-UBI (50 μg) was radiolabeled with pure Ga-68 (500MBq) by incubating the reaction mixture at pH 4.5 for 10 min, 95°C. Rats were infected with Staph-A at the hind leg joint of rats to form bacterial abscess. Sterile inflammation was induced in the right thigh muscle by injecting 200 μl of 100% turpentine oil. Rats were injected intravenously with 10-15 MBq of tracer, and images were acquired at different time intervals with Siemens (Biograph mCT) positron emission tomography computed tomography scanner. The early images at 6 min postinjection clearly indicated mild uptake of the agent corresponding to the infection site, which increased dramatically at 20, 30, and 60 min postinjection. The target to background ratio (T/B) increased significantly over the same time period of study (1.6, 4.2, and 6.1, respectively). There was a mild uptake of 68Ga-DOTA-UBI at the site corresponding to sterile inflammation at 6 min postinjection, which was rapidly washed off as seen at 25 and 45 min images. The images indicated fast clearance of the agent from liver and soft tissues within 6 min. Control rats showed similar biodistribution of activity. The mild uptake of 68Ga-DOTA-UBI at the corresponding Staph-A infection lesion and very fast kinetics of clearance from the blood pool and soft tissues suggested a very high clinical potential for this agent. The absence of uptake of the agent at sterile inflammation site suggests that the agent may be useful in distinguishing infection from inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
30. DIAGNOSTIC ACCURACY OF TC-99M LABELLED UBIQUICIDIN (29-41) SPECT/CT FOR DIAGNOSIS OF OSTEOMYELITIS IN DIABETIC FOOT.
- Author
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Atif, Muhammad, Hussain, Fida, Dar, Zaigham Salim, Khatoon, Jameela, Ajmal, Saadia, and Adil, Muhammad
- Subjects
OSTEOMYELITIS ,DIABETIC foot ,COMPUTED tomography ,SINGLE-photon emission computed tomography - Abstract
Objective: To determine diagnostic accuracy of Tc-99m labelled Ubiquicidin (29-41) SPECT/CT for detection of osteomyelitis in diabetic foot patients by taking bone biopsy as gold standard. Study Design: Cross-sectional validation study. Place and Duration of Study: Nuclear Medical Centre, Armed Forces Institute of Pathology, from Apr 2017 to Mar 2018. Methodology: Study assessed 122 patients of both genders, aged between 30-80 years (mean age=55.3 years), presenting with diabetic foot ulcers having suspicion of osteomyelitis, by Tc-99m-Ubiquicidin (29-41) SPECT/CT followed by bone biopsy (histopathology and culture) taken as gold standard. Results: Among 122 patients [94 male (77%) and 28 female (23%)], osteomyelitis was histopathologically confirmed in 113 patients. 107 out of these patients were positive for osteomyelitis on Tc-99m-UBI (29-41) SPECT/CT (true positives) while 6 were false negative. Out of 9 patients declared negative for osteomyelitis on histopathology and culture, 8 were negative on Tc-99m-UBI (29-41) SPECT/CT as well (true negative) while only 1 case came out to be positive (false positive). Thus, the Tc-99m-UBI (29-41) scan showed 94.6% sensitivity, 88.89% specificity, 99% positive predictive value, 57% negative predictive value with overall 94.2% diagnostic accuracy. Conclusion: Tc-99m labelled Ubiquicidin (29-41) SPECT/CT scan can precisely localize infective focus, in diabetic foot osteomyelitis, with simultaneous discrimination between bone and soft tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Update on functional imaging in the evaluation of diabetic foot infection.
- Author
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Iyengar, Karthikeyan P., Jain, Vijay K., Awadalla Mohamed, Muyed Kamal, Vaishya, Raju, and Vinjamuri, Sobhan
- Abstract
Diabetic foot infection is a preventable complication of diabetes mellitus. It is an essential component of diabetic foot disease, which is characterised by a triad of neuropathy, ischaemia and infection. These factors may lead to foot ulceration, sepsis and amputation resulting in increased morbidity and poor quality of life. Confirming or excluding infection can be difficult especially when routine laboratory tests and plain radiographs are inconclusive. Early diagnosis and localization of diabetic foot infection is extremely important to institute timely, appropriate therapy. Structural imaging using computed tomography and magnetic resonance imaging all have individual applications towards the diagnostic workup of this condition but have their own limitations. Scintigraphic detection is based on physiochemical changes and hence provides a functional evaluation of bone pathology. We describe the evolution of functional nuclear medicine imaging including immunoscintigraphy in diabetic foot infection and highlight current applications of physiological 18-Fluoro-deoxyglucose positron emission tomography (18-FDG-PET) and computed tomography (18-FDG-PET/CT) in such patients. 18-FDG-PET/CT is a promising modality for imaging diabetic foot infection. Future studies will allow standardisation of technological details and options of 18-FDG-PET/CT interpretation in diabetic foot infection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
32. [99mTc‐HYNIC/EDDA]‐MccJ25 antimicrobial peptide analog as a potential radiotracer for detection of infection.
- Author
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Mazaheri Tehrani, Maryam, Erfani, Mostafa, and Amirmozafari, Nour
- Subjects
- *
RADIOACTIVE tracers , *RADIOCHEMICAL purification , *BLADDER , *ANTIMICROBIAL peptides , *NUCLEAR medicine , *PEPTIDE derivatives , *INJECTIONS - Abstract
Bacterial infections are a serious risk to human health, and therefore techniques for early detection of infectious foci need to be further developed to begin treatment quickly and achieve better results. Antimicrobial peptides labeled with gamma‐emission radio nuclides are important diagnostic radiotracers in nuclear medicine. This study was conducted to evaluate the potential of a 99mTc‐labeled MicrocinJ25 (MccJ25) antimicrobial peptide analog for early detection of infection. For this purpose, a HYNIC conjugated cyclic peptide derivative based on the primary structure of MccJ25 peptide was prepared and labeled by 99mTc with tricine and EDDA as coligands. The [99mTc‐HYNIC/EDDA]‐MccJ25 peptide analog showed high radiochemical purity (˃90% (n = 5)) which was stable up to 24 hr after labeling. The radiotracer showed specific uptake to the Escherichia coli (E. coli) bacterial (40.45 ± 5.21%) at 1 hr incubation. High kidneys uptake of radioactivity (4.71 ± 0.84% and 3.76 ± 0.45% ID/g at 1 and 4 hr after injection respectively) demonstrates that most of the whole body clearance was proceeded via the urinary system. Significant radioactivity uptake (1.71 ± 0.34%ID/g) was observed in thigh muscle of mouse with E. coli induced infection at 1 hr after injection. In the blocking test, due to the significant decrease of radioactivity uptake in the infection site (0.62 ± 0.21%ID/g after 1 hr), the specificity of infection uptake was reviled. Despite the high activity of the bladder due to urinary excretion, the infected area was somewhat visible. Hence, the results indicate the potential of this new radiotracer to be used as a diagnostic agent in E. coli infections. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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33. Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model: a feasibility study for clinical diagnosis of prosthetic joint infections.
- Author
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Schoenmakers, Jorrit W. A., Heuker, Marjolein, López-Álvarez, Marina, Nagengast, Wouter B., van Dam, Gooitzen M., van Dijl, Jan Maarten, Jutte, Paul C., and van Oosten, Marleen
- Subjects
- *
JOINT infections , *ARTIFICIAL joints , *ARTIFICIAL knees , *DIAGNOSIS , *BIOFILMS , *FEASIBILITY studies - Abstract
Purpose: Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints. Methods: Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses. Results: We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW. Conclusion: The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
34. [ 68 Ga]Ga-Schizokinen, a Potential Radiotracer for Selective Bacterial Infection Imaging.
- Author
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Akter A, Firth G, Darwesh AMF, Cooper MS, Chuljerm H, Cilibrizzi A, Blower PJ, Hider RC, Lyons O, Schelenz S, Mehra V, and Abbate V
- Subjects
- Animals, Mice, Humans, Positron Emission Tomography Computed Tomography methods, Tissue Distribution, Positron-Emission Tomography methods, Female, Bacteria, Ribosomal Proteins, Gallium Radioisotopes chemistry, Bacterial Infections diagnostic imaging, Bacterial Infections microbiology, Radiopharmaceuticals chemistry, Radiopharmaceuticals pharmacokinetics
- Abstract
Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([
68 Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [68 Ga]Ga-SKN by Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and S. epidermidis , but no uptake by Candida glabrata , C. albicans , or Aspergillus fumigatus , demonstrated its specificity to bacterial species. Whole-body [68 Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [68 Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.- Published
- 2024
- Full Text
- View/download PDF
35. Vasogenic Edema Covering the Brain Surface in a Case of Severe Meningoencephalitis Due to Varicella-Zoster Virus Infection.
- Author
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Fujiwara S, Ando K, Tsunogae M, Arizono S, and Kawamoto M
- Abstract
Meningoencephalitis caused by varicella-zoster virus (VZV) is a serious condition requiring prompt antiviral treatments, but magnetic resonance imaging (MRI) findings are often normal, limiting early diagnostic utility. We report a case of severe VZV-associated meningoencephalitis characterized by diffuse T2 hyperintense lesions covering the brain surface on MRI, presumed to be vasogenic edema. An immunocompetent 78-year-old Japanese woman presented with a disturbance of consciousness preceded by seven days of headache. On admission, she was in a semi-coma with intermittent convulsive seizures and had a localized skin rash with blisters on her back. Brain MRI showed diffuse T2 hyperintensity on the brain surface with an elevated apparent diffusion coefficient and the marked gadolinium-contrast enhancement of the pia-arachnoid membrane and vessel walls. Polymerase chain reaction using cerebrospinal fluid revealed the presence of VZV, and then she was diagnosed with VZV-associated meningoencephalitis. Treatment with acyclovir and corticosteroids was initiated, leading to some clinical improvement; however, the patient developed acute non-occlusive mesenteric ischemia and died on the 10th day of hospitalization. The characteristic MRI findings observed in our patient may be useful in considering the pathogenesis and early diagnosis of this rare entity., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Fujiwara et al.)
- Published
- 2024
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36. Infection Imaging
- Author
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Klingensmith, William C., III and Klingensmith III, William C
- Published
- 2016
- Full Text
- View/download PDF
37. Towards clinical application of non-invasive imaging to detect bacterial infections
- Author
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Knut Ohlsen and Tobias Hertlein
- Subjects
fluorescence imaging ,imaging probes ,in vivo imaging ,infection imaging ,magnetic resonance imaging ,molecular imaging ,PET imaging ,Staphylococcus aureus infections ,Infectious and parasitic diseases ,RC109-216 - Abstract
In vivo imaging technologies offer a great potential for the diagnosis of difficult-to-treat bacterial infections. A major limitation of conventional imaging modalities is the lack of specificity to distinguish the site of bacterial infection from sterile inflammation. Targeted approaches like antibiotics linked to imaging tracers for detection of various bacterial pathogens or species-specific antibodies combined with anatomical imaging modalities are currently being evaluated to overcome this problem. Considering the recent progress in optical and targeted imaging that may accelerate preclinical development programs, clinical implementation of in vivo imaging modalities to detect bacterial infection foci becomes realistic in the future.
- Published
- 2018
- Full Text
- View/download PDF
38. Modifying the Siderophore Triacetylfusarinine C for Molecular Imaging of Fungal Infection.
- Author
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Kaeopookum, Piriya, Summer, Dominik, Pfister, Joachim, Orasch, Thomas, Lechner, Beatrix E., Petrik, Milos, Novy, Zbynek, Matuszczak, Barbara, Rangger, Christine, Haas, Hubertus, and Decristoforo, Clemens
- Subjects
- *
MYCOSES , *POSITRON emission tomography , *PROTEIN binding , *ASPERGILLUS fumigatus , *FUNGAL cultures , *PULMONARY aspergillosis - Abstract
Purpose: Aspergillus fumigatus produces the siderophore triacetylfusarinine C (TAFC) for iron acquisition which is essential for its virulence. Therefore, TAFC is a specific marker for invasive aspergillosis. We have shown previously that positron emission tomography (PET) imaging with [68Ga]TAFC exhibited excellent targeting properties in an A. fumigatus rat infection model. In this study, we aimed to prepare TAFC analogs modifying fusarinine C (FSC) by acylation with different carbon chain lengths as well as with charged substituents and investigated the influence of introduced substituents on preservation of TAFC characteristics in vitro and in vivo.Procedures: Fifteen TAFC derivatives were prepared and labeled with gallium-68. In vitro uptake assays were carried out in A. fumigatus under iron-replete as well as iron-depleted conditions and distribution coefficient was determined. Based on these assays, three compounds, [68Ga]tripropanoyl(FSC) ([68Ga]TPFC), [68Ga]diacetylbutanoyl(FSC) ([68Ga]DABuFC), and [68Ga]trisuccinyl(FSC) ([68Ga]FSC(suc)3), with high, medium, and low in vitro uptake in fungal cultures, were selected for further evaluation. Stability and protein binding were evaluated and in vivo imaging performed in the A. fumigatus rat infection model.Results: In vitro uptake studies using A. fumigatus revealed specific uptake of mono- and trisubstituted TAFC derivatives at RT. Lipophilicities as expressed by logD were 0.34 to - 3.80. The selected compounds displayed low protein binding and were stable in PBS and serum. Biodistribution and image contrast in PET/X-ray computed tomography of [68Ga]TPFC and [68Ga]DABuFC were comparable to [68Ga]TAFC, whereas no uptake in the infected region was observed with [68Ga]FSC(suc)3.Conclusions: Our studies show the possibility to modify TAFC without losing its properties and specific recognition by A. fumigatus. This opens also new ways for multimodality imaging or theranostics of fungal infection by introducing functionalities such as fluorescent dyes or antifungal moieties. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
39. 99mTc-amoxicillin: A novel radiopharmaceutical for infection imaging.
- Author
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Shahzadi, Syeda Kiran, Qadir, Muhammad Abdul, Shabnam, Shahzad, and Javed, Muhammad
- Abstract
Amoxicillin, a penicillin derivative was synthesized as ready-to-used single vial kit and radiolabeled with technetium-99m. Various trials have been carried out to optimize the concentration of stannous chloride, amoxicillin, pH and reaction time. Radiochemical purity, in vitro and in vivo stability, partition co-efficient, protein binding and biodistribution in rabbit infected with Streptococcus pneumoniae were studied. The biodistribution studies in rabbit showed that
99m Tc-amoxicillin started to accumulate in the infected area at 1-h postadministration.99m Tc-amoxicillin may prove itself as potential novel radiopharmaceutical for imaging infections caused by many bacteria. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
40. Comparison of DOTA and NODAGA as chelates for 68Ga-labelled CDP1 as novel infection PET imaging agents.
- Author
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Mdlophane, A. H., Ebenhan, T., Marjanovic-Painter, B., Govender, T., Sathekge, M. M., and Zeevaart, J. R.
- Subjects
- *
BACTERIAL cell walls , *RADIOACTIVE tracers , *PROTEIN binding , *INFECTION , *CHELATES , *PEPTIDE antibiotics - Abstract
The cathelicidin-derived peptide (CDP1) is a human antimicrobial peptide that preferentially targets bacterial membranes in response to infection. CDP1 was functionalised with NODAGA and DOTA for complexation with gallium-68 to evaluate its potential as an infection imaging tracer. The synthesis of [68Ga]Ga–NODAGA–CDP1 and [68Ga]Ga–DOTA–CDP1 were optimised for pH, molarity, incubation time and temperature, and product purification. The integrity and protein binding were investigated employing [68Ga]GaCl3 and [68Ga]Ga–DOTA–TATE as internal references. [68Ga]Ga–NODAGA–CDP1 displayed good labelling properties with higher product yield compared to [68Ga]Ga–DOTA–CDP1. In contrast, [68Ga]Ga–DOTA–CDP1 showed better stability and is the preferred candidate for an in vivo investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
41. Utility of FDG-PET/CT for the Detection and Characterization of Sternal Wound Infection Following Sternotomy.
- Author
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Hariri, Hadi, Tan, Stéphanie, Martineau, Patrick, Lamarche, Yoan, Carrier, Michel, Finnerty, Vincent, Authier, Sébastien, Harel, Francois, and Pelletier-Galarneau, Matthieu
- Abstract
Purpose: FDG-PET/CT has the potential to play an important role in the diagnosis of sternal wound infections (SWI). The purpose of this study was to analyze the diagnostic accuracy of FDG-PET/CT for SWI in patients following sternotomy. Methods: We performed a single-center, retrospective analysis of patients who had undergone median sternotomy and FDG-PET/CT imaging. The gold standard consisted of positive bacterial culture and/or the presence of purulent material at surgery. Qualitative patterns of sternal FDG uptake, SUV
max , and associated CT findings were determined, and an imaging scoring system was developed. The diagnostic performances were studied in both the recent (≤ 6 months between sternotomy and imaging) and remote surgery phase (> 6 months). Results: A total of 40 subjects were identified with 11 confirmed SWI cases. Consensus interpretation was associated with a sensitivity of 91% and specificity of 97%. Combination of uptake patterns yielded an AUC of 0.96 while use of SUVmax yielded an AUC of 0.82. Conclusions: Results suggest that FDG-PET/CT may be useful for the diagnosis of SWI with optimal diagnostic accuracy achieved by identifying specific patterns of uptake. SUVmax can be helpful in assessing subjects with remote surgery, but its use is limited in the context of recent surgery. Further studies are required to confirm these results. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
42. Enteropathogenic Escherichia coli remodels host endosomes to promote endocytic turnover and breakdown of surface polarity.
- Author
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Kassa, Ephrem G., Zlotkin-Rivkin, Efrat, Friedman, Gil, Ramachandran, Rachana P., Melamed-Book, Naomi, Weiss, Aryeh M., Belenky, Michael, Reichmann, Dana, Breuer, William, Pal, Ritesh Ranjan, Rosenshine, Ilan, Lapierre, Lynne A., Goldenring, James R., and Aroeti, Benjamin
- Subjects
- *
ENDOCYTOSIS , *ENDOSOMES , *BACTERIAL proteins , *ESCHERICHIA coli , *MEMBRANE proteins , *BLOOD proteins - Abstract
Enteropathogenic E. coli (EPEC) is an extracellular diarrheagenic human pathogen which infects the apical plasma membrane of the small intestinal enterocytes. EPEC utilizes a type III secretion system to translocate bacterial effector proteins into its epithelial hosts. This activity, which subverts numerous signaling and membrane trafficking pathways in the infected cells, is thought to contribute to pathogen virulence. The molecular and cellular mechanisms underlying these events are not well understood. We investigated the mode by which EPEC effectors hijack endosomes to modulate endocytosis, recycling and transcytosis in epithelial host cells. To this end, we developed a flow cytometry-based assay and imaging techniques to track endosomal dynamics and membrane cargo trafficking in the infected cells. We show that type-III secreted components prompt the recruitment of clathrin (clathrin and AP2), early (Rab5a and EEA1) and recycling (Rab4a, Rab11a, Rab11b, FIP2, Myo5b) endocytic machineries to peripheral plasma membrane infection sites. Protein cargoes, e.g. transferrin receptors, β1 integrins and aquaporins, which exploit the endocytic pathways mediated by these machineries, were also found to be recruited to these sites. Moreover, the endosomes and cargo recruitment to infection sites correlated with an increase in cargo endocytic turnover (i.e. endocytosis and recycling) and transcytosis to the infected plasma membrane. The hijacking of endosomes and associated endocytic activities depended on the translocated EspF and Map effectors in non-polarized epithelial cells, and mostly on EspF in polarized epithelial cells. These data suggest a model whereby EPEC effectors hijack endosomal recycling machineries to mislocalize and concentrate host plasma membrane proteins in endosomes and in the apically infected plasma membrane. We hypothesize that these activities contribute to bacterial colonization and virulence. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
43. SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [125I]anti-C3d mAb.
- Author
-
Foss, Catherine A., Kulik, Liudmila, Ordonez, Alvaro A., Jain, Sanjay K., Michael Holers, V., Thurman, Joshua M., and Pomper, Martin G.
- Subjects
- *
MYCOBACTERIAL diseases , *MYCOBACTERIUM tuberculosis , *SINGLE-photon emission computed tomography , *IMMUNOFLUORESCENCE , *BACTERIAL diseases , *EPITHELIAL cells - 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. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
44. Susceptibility of 99mTc-Ciprofloxacin for Common Infection Causing Bacterial Strains Isolated from Clinical Samples: an In Vitro and In Vivo Study.
- Author
-
Naqvi, Syed Ali Raza, Roohi, Samina, Sabir, Hassina, Shahzad, Sohail Anjum, Aziz, Aysha, and Rasheed, Rashid
- Abstract
99m Tc-ciprofloxacin scintigraphy is useful in the detection of gram-positive and gram-negative bacterial infections and also for differentiating the infection from aseptic inflammation. However, due to growing bacterial resistance to antibiotics, the99m Tc-ciprofloxacin no longer can be effective in broad-spectrum infection imaging as it is gradually losing specificity. In this study, we are presenting our findings regarding the in vitro and in vivo susceptibility of99m Tc-ciprofloxacin for multi-drug-resistant Staphylococcus aurous, Escherichia coli, and Pseudomonas aeruginosa bacterial strains which were isolated from clinical samples. The results of radiosynthesis of99m Tc-ciprofloxacin showed more the 95% radiochemical purity and less than 5% radioactive impurities. In vitro99m Tc-ciprofloxacin susceptibility test showed that E. coli offered more resistant to99m Tc-ciprofloxacin as compared to S. aurous and P. aeruginosa. In vivo study using bacterial infection induced rabbit model also revealed lowest uptake by E. coli lesion. The T/NT values were obtained 1.96 ± 0.15 in the case of E. coli; 2.81 ± 0.51 in the case of S. aurous; and 2.32 ± 0.66 in the case of P. aeruginosa at 4 h post-injection. The SPECT infection imaging of S. aurous, E. coli, and P. aeruginosa bacterial infection induced rabbit models also indicated the clear accumulation in S. aurous and P. aeruginosa lesions while negligible uptake by E. coli lesion further verify the in vitro and in vivo susceptibility profile. On the bases of the results obtained, the99m Tc-ciprofloxacin showed selective and poor broad spectrum SPECT infection imaging. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
45. Technetium-99m labeled Ibuprofen: Development and biological evaluation using sterile inflammation induced animal models.
- Author
-
Khan, Naeem-Ul-Haq, Naqvi, Syed Ali Raza, Sohail, Hamza, Roohi, Samina, and Jamal, Muhammad Asghar
- Abstract
In this study we are presenting the development of technetium-99m (
99m Tc) labeled ibuprofen for the imaging of aseptic inflammation.99m Tc-Ibuprofen complex was developed by optimizing the radiolabeling conditions such as reaction time, ligand and reducing agent concentration, pH, reaction time and temperature. Following the addition of 600 µg of ibuprofen, 4 µg of stannous chloride as reducing agent and 300 MBq99m Tc radioactivity; the pH of reaction mixture was adjusted to 11 and allowed to react for 15 min at room temperature. Chromatography analysis revealed > 94%99m Tc-ibuprofen complex formation with promising stability in saline and blood serum up to 6 h. Biodistribution study using normal and sterile inflammation induced mice indicated low accumulation of labeled compound in key body organs; however, kidneys (14.76 ± 0.87% ID/g organ) and bladder (31.6 ± 3.0% ID/g organ) showed comparatively higher radioactivity due to main excretory path. Inflamed to normal tissues ratio (T/NT), at 1 h post-injection, showed promising value (4.57 ± 0.56). The SPECT imaging of artificially inflammation induced rabbit model also verified the biodistribution results. In conclusion, radiochemical purity and biological evaluation of99m Tc-ibuprofen complex indicates the agent can be utilized for imaging of deep seated aseptic inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
46. ZAP’s stress granule localization is correlated with its antiviral activity and induced by virus replication.
- Author
-
Law, Lok Man John, Razooky, Brandon S., Li, Melody M. H., You, Shihyun, Jurado, Andrea, Rice, Charles M., and MacDonald, Margaret R.
- Subjects
- *
ZINC-finger proteins , *VIRAL replication , *VIRUS diseases , *ANTIVIRAL agents , *SINDBIS virus , *MESSENGER RNA - Abstract
Cellular antiviral programs encode molecules capable of targeting multiple steps in the virus lifecycle. Zinc-finger antiviral protein (ZAP) is a central and general regulator of antiviral activity that targets pathogen mRNA stability and translation. ZAP is diffusely cytoplasmic, but upon infection ZAP is targeted to particular cytoplasmic structures, termed stress granules (SGs). However, it remains unclear if ZAP’s antiviral activity correlates with SG localization, and what molecular cues are required to induce this localization event. Here, we use Sindbis virus (SINV) as a model infection and find that ZAP’s localization to SGs can be transient. Sometimes no apparent viral infection follows ZAP SG localization but ZAP SG localization always precedes accumulation of SINV non-structural protein, suggesting virus replication processes trigger SG formation and ZAP recruitment. Data from single-molecule RNA FISH corroborates this finding as the majority of cells with ZAP localization in SGs contain low levels of viral RNA. Furthermore, ZAP recruitment to SGs occurred in ZAP-expressing cells when co-cultured with cells replicating full-length SINV, but not when co-cultured with cells replicating a SINV replicon. ZAP recruitment to SGs is functionally important as a panel of alanine ZAP mutants indicate that the anti-SINV activity is correlated with ZAP’s ability to localize to SGs. As ZAP is a central component of the cellular antiviral programs, these data provide further evidence that SGs are an important cytoplasmic antiviral hub. These findings provide insight into how antiviral components are regulated upon virus infection to inhibit virus spread. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
47. Synthesis and Evaluation of Novel Norfloxacin Isonitrile 99mTc Complexes as Potential Bacterial Infection Imaging Agents
- Author
-
Si’an Fang, Yuhao Jiang, Di Xiao, Xuran Zhang, Qianqian Gan, Qing Ruan, and Junbo Zhang
- Subjects
norfloxacin ,isonitriles ,quinolones ,technetium-99m ,infection imaging ,Pharmacy and materia medica ,RS1-441 - Abstract
To develop potential technetium-99m single-photon emission computed tomography (SPECT) imaging agents for bacterial infection imaging, the novel norfloxacin isonitrile derivatives CN4NF and CN5NF were synthesized and radiolabeled with a [99mTc][Tc(I)]+ core to obtain [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF. These compounds were produced in high radiolabeling yields and showed hydrophilicity and good stability in vitro. The bacterial binding assay indicated that [99mTc]Tc-CN4NF and [99mTc]Tc-CN5NF were specific to bacteria. Compared with [99mTc]Tc-CN4NF, biodistribution studies of [99mTc]Tc-CN5NF showed a higher uptake in bacteria-infected tissues than in turpentine-induced abscesses, indicating that [99mTc]Tc-CN5NF could distinguish bacterial infection from sterile inflammation. In addition, [99mTc]Tc-CN5NF had higher abscess/blood and abscess/muscle ratios. SPECT image of [99mTc]Tc-CN5NF showed that there was a clear accumulation in the infection site, suggesting that it could be a potential bacterial infection imaging radiotracer.
- Published
- 2021
- Full Text
- View/download PDF
48. In Vitro and In Vivo Evaluation of 99mTc-Polymyxin B for Specific Targeting of Gram-Bacteria
- Author
-
Sveva Auletta, Filippo Galli, Michela Varani, Giuseppe Campagna, Martina Conserva, Daniela Martinelli, Iolanda Santino, and Alberto Signore
- Subjects
polymyxin B ,infection imaging ,bacteria ,99mTc-polymyxin B ,Microbiology ,QR1-502 - Abstract
Background: Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of 99mTc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria. Results: Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice, 99mTc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of 99mTc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls. Conclusions: In vitro and in vivo results suggest that 99mTc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of 99mTc-HYNIC-PMB in other animal models and in humans.
- Published
- 2021
- Full Text
- View/download PDF
49. Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent
- Author
-
Si’an Fang, Yuhao Jiang, Qianqian Gan, Qing Ruan, Di Xiao, and Junbo Zhang
- Subjects
ciprofloxacin xanthate ,quinolones ,infection imaging ,99mTc-radiolabeling ,Organic chemistry ,QD241-441 - Abstract
In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.
- Published
- 2020
- Full Text
- View/download PDF
50. Infected cyst in patients with autosomal dominant polycystic kidney disease: Analysis of computed tomographic and ultrasonographic imaging features.
- Author
-
Oh, Jiseon, Shin, Cheong-Il, and Kim, Sang Youn
- Subjects
- *
POLYCYSTIC kidney disease , *COMPUTED tomography , *CYSTS (Pathology) , *ULTRASONIC imaging , *RETROSPECTIVE studies - Abstract
Purpose: To investigate the imaging features of cyst infection in autosomal dominant polycystic kidney disease (ADPKD) patients using computed tomography (CT) and ultrasonography (US). Materials & methods: The institutional review board approved this retrospective study. Fifty-one episodes with proven cyst infection in forty-three ADPKD patients were included. Two experienced abdominal radiologists reviewed CT and US images and evaluated the following imaging features in consensus: cyst size, location, cyst shape, intracystic attenuation, intracystic echogenicity, intracystic heterogeneity, wall thickness, the presence of fluid-fluid level, septation, intracystic gas, pericystic fat infiltration, and pericystic hyperemia. Intracystic attenuation was measured for all infected cysts and two presumed normal cysts and compared using the Wilcoxon rank-sum test. Results: On CT scans, the median size of infected cysts was 5.5 cm (range: 2.3–18.8 cm) and 46 of 51 (90.2%) infected cysts were located in the subcapsular region. Most (48 of 51, 94.1%) infected cysts showed lobulated, focal bulging or irregular shape. Discernible wall thickening (84.1%) was the most frequently found imaging feature of infected cysts followed by relatively higher intracystic attenuation compared to normal cysts (79.1%) and pericystic fat infiltration (52.9%). Fluid/fluid level was found in 3 of 51 (5.9%) infected cysts and intracystic gas was found in 3 of 51 (5.9%) infected cysts, respectively. For hepatic cysts, 11 of 14 (78.6%) infected cysts showed pericystic hyperemia. Intracystic attenuation was significantly higher in infected cysts (median; 19.0 HU) than in presumed normal cysts (median; 8.5 HU) (P<0.001), and exceeded 25 HU in 18 (35.3%) of 51 infected cysts. Among the 41 infected cysts for which US images were available, 35 (85.1%) showed heterogeneous echogenicity. Conclusion: Minute imaging features such as minimal wall thickening or relatively high attenuation compared to normal cysts would be helpful to detect infected cysts in ADPKD patients. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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