Comparison of 99mTc- and 18F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

Salber, Dagmar; Gunawan, Johannes; Langen, Karl‐Josef; Fricke, Eva; Klauth, Peter; Burchert, Wolfgang; Zijlstra, S.

doi:10.2967/jnumed.108.050880

Cited by 16 publications

(12 citation statements)

References 8 publications

(10 reference statements)

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“…As radiopharmaceuticals are mostly administered by i.v. injection, the peptides can be prone to enzymatic degradation or the destabilisation of the radioisotope as reported for 18 F-UBI29-41 [66]. The lactoferrin-derived peptide hLF(1-11) showed great sensitivity as infection agent targeting multidrug-resistant Acinetobacter baumannii strains; however binding to Candida albicans , a fungus, and the hepatobiliar excretion made it less favourable for imaging [51].…”

Section: Discussion and Perspectivementioning

confidence: 99%

Antimicrobial Peptides: Their Role as Infection-Selective Tracers for Molecular Imaging

Ebenhan

Gheysens

Kruger

et al. 2014

BioMed Research International

173

141

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Antimicrobial peptides (AMPs) are a heterogeneous class of compounds found in a variety of organisms including humans and, so far, hundreds of these structures have been isolated and characterised. They can be described as natural microbicide, selectively cytotoxic to bacteria, whilst showing minimal cytotoxicity towards the mammalian cells of the host organism. They act by their relatively strong electrostatic attraction to the negatively charged bacterial cells and a relatively weak interaction to the eukaryote host cells. The ability of these peptides to accumulate at sites of infection combined with the minimal host's cytotoxicity motivated for this review to highlight the role and the usefulness of AMPs for PET with emphasis on their mechanism of action and the different interactions with the bacterial cell. These details are key information for their selective properties. We also describe the strategy, design, and utilization of these peptides as potential radiopharmaceuticals as their combination with nuclear medicine modalities such as SPECT or PET would allow noninvasive whole-body examination for detection of occult infection causing, for example, fever of unknown origin.

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Section: Discussion and Perspectivementioning

confidence: 99%

Antimicrobial Peptides: Their Role as Infection-Selective Tracers for Molecular Imaging

Ebenhan

Gheysens

Kruger

et al. 2014

BioMed Research International

173

141

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“…Radiolabelled synthetic fragments of ubiquicidin (UBI), a naturally occurring human antimicrobial peptide that targets bacteria, possess the ability to differentiate infection from sterile inflammation [106]. Moreover, it seems to be that the amount of radiolabelled UBI 29-41 uptake depends on the number of viable bacteria present at the site of infection, but results of recent data, performed in animal models of several infections (including PJI), are more controversial [107][108][109][110][111]. Nevertheless, first studies of this agent for diagnosing PJI in humans are encouraging [112].…”

Section: Investigational/experimental Tracersmentioning

confidence: 99%

Prosthetic joint infections: radionuclide state-of-the-art imaging

Gemmel¹,

Wyngaert²,

Love

et al. 2012

Eur J Nucl Med Mol Imaging

165

151

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Prosthetic joint replacement surgery is performed with increasing frequency. Overall the incidence of prosthetic joint infection (PJI) and subsequently prosthesis revision failure is estimated to be between 1 and 3%. Differentiating infection from aseptic mechanical loosening, which is the most common cause of prosthetic failure, is especially important because of different types of therapeutic management. Despite a thorough patient history, physical examination, multiple diagnostic tests and complex algorithms, differentiating PJI from aseptic loosening remains challenging. Among imaging modalities, radiographs are neither sensitive nor specific and cross-sectional imaging techniques, such as computed tomography and magnetic resonance imaging, are limited by hardware-induced artefacts. Radionuclide imaging reflects functional rather than anatomical changes and is not hampered by the presence of a metallic joint prosthesis. As a result scintigraphy is currently the modality of choice in the investigation of suspected PJI. Unfortunately, there is no true consensus about the gold standard technique since there are several drawbacks and limitations inherent to each modality. Bone scintigraphy (BS) is sensitive for identifying the failed joint replacement, but cannot differentiate between infection and aseptic loosening. Combined bone/gallium scintigraphy (BS/GS) offers modest improvement over BS alone for diagnosing PJI. However, due to a number of drawbacks, BS/GS has generally been superseded by other techniques but it still may have a role in neutropenic patients. Radiolabelled leucocyte scintigraphy remains the gold standard technique for diagnosing neutrophil-mediated processes. It seems to be that combined in vitro labelled leucocyte/bone marrow scintigraphy (LS/BMS), with an accuracy of about 90%, is currently the imaging modality of choice for diagnosing PJI. There are, however, significant limitations using in vitro labelled leucocytes and considerable effort has been devoted to developing alternative radiotracers, such as radiolabelled HIGs, liposomes, antigranulocyte antibodies and fragments, as well as more investigational tracers such as radiolabelled antibiotics, antimicrobial peptides, bacteriophages and thymidine kinase. On the other hand, positron emission tomography (PET) is still growing in the field of PJI imaging with radiotracers such as (18)F-fluorodeoxyglucose (FDG), (18)F-FDG white blood cells and (18)F-fluoride. But unfortunately this superb tomographic technique will only receive full acceptance when specific PET uptake patterns can be successfully developed. The emergence of hybrid modality imaging using integrated single photon emission computed tomography (SPECT) and PET with computed tomography (SPECT/CT and PET/CT) may also have a contributing role for more accurate assessment of joint replacement complications, especially combined with new radiotracers such as (68)Ga and (64)Cu. Finally, in searching for infection-specific tracers, currently there is no such diagnostic agent available.

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“…3A). This antibody has been used by others [43], [44], [45]. The numbers of glomerular and tubulointerstitial macrophages were significantly higher in STZ vs. control (9.4±0.9 vs. 2±0.4 and 46.1±10.3 vs. 7.1±0.6), and Spironolactone treatment significantly decreased the number of ED-1 + cells in SP rats (3.1±0.4, and 13.4±3.5) (Fig.…”

Section: Resultsmentioning

confidence: 88%

Spironolactone Rescues Dot1a-Af9-Mediated Repression of Endothelin-1 and Improves Kidney Injury in Streptozotocin-Induced Diabetic Rats

Zhou

Liu

H³

et al. 2012

PLoS ONE

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The molecular mechanism linking aldosterone and endothelin-1 in the development of diabetic nephropathy has not been completely elucidated. Here, we provide evidence showing that streptozotocin-induced diabetic rats have significantly increased aldosterone and endothelin-1 in the kidney tissue and markedly decreased expression of Dot1a and Af9. Blocking aldosterone with spironolactone significantly reduced proteinuria, glomerulosclerosis, tubulointerstitial injury and endothelin-1 expression, and significantly increased Dot1a and Af9 expression. Increasing Dot1a and Af9 expression by spironolactone or by stable transfection led to impaired endothelin-1 expression in NRK-52 cells. In contrast, downregulation of Dot1a and Af9 by aldosterone in NRK-52E cells caused upregulation of endothelin-1. Genetic inactivation of Dot1l, which encodes Dot1a, in Aqp2-expressing principal cells of mouse kidney impaired association of Dot1a and H3 dimethyl K79 with the specific subregions of endothelin-1 promoter, and upregulates endothelin-1 mRNA and protein expression. Our data suggest that Dot1a and Af9 repress endothelin-1 in vitro and in vivo. Excessive aldosterone induces kidney injury, in part possibly by downregulating Dot1a and Af9, and thus relieving Dot1a-Af9-mediated repression to increase endothelin-1 transcription. Spironolactone ameliorates kidney injury in Streptozotocin-induced diabetic rats, possibly by restoring Dot1a-Af9-mediated repression to reduce endothelin-1 expression. Therefore, Dot1a and Af9 as aldosterone-downregulated targets are negative regulators of endothelin-1 transcription in vitro and in vivo, and may be considered as new potential therapeutic targets of kidney injury in diabetes.

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Comparison of ^99mTc- and ¹⁸F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

Cited by 16 publications

References 8 publications

Antimicrobial Peptides: Their Role as Infection-Selective Tracers for Molecular Imaging

Antimicrobial Peptides: Their Role as Infection-Selective Tracers for Molecular Imaging

Prosthetic joint infections: radionuclide state-of-the-art imaging

Spironolactone Rescues Dot1a-Af9-Mediated Repression of Endothelin-1 and Improves Kidney Injury in Streptozotocin-Induced Diabetic Rats

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