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

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Thomas Ebenhan ◽  
Olivier Gheysens ◽  
Hendrick Gert Kruger ◽  
Jan Rijn Zeevaart ◽  
Mike Machaba Sathekge

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.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Anoshirwan Andrej Tavakoli ◽  
Miriam Reichert ◽  
Tanja Blank ◽  
Dietmar Dinter ◽  
Sabine Weckbach ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 182-183
Author(s):  
S. Signa ◽  
R. Caorsi ◽  
G. Stagnaro ◽  
F. Minoia ◽  
P. Picco ◽  
...  

Background:Whole-body magnetic resonance imaging (WBMRI) is a fast and accurate method to detect diseases throughout the entire body without exposure to ionizing radiation. Possible emerging applications for this technique include rheumatologic field and evaluation of fever of unknown origin (FUO).Objectives:To evaluate the ability of WBMRI to identify significant potential diagnostic clue (PDC) in patients presenting a non specific inflammatory clinical picture.Methods:We retrospectively collected cases of pediatric patients followed in a single pediatric rheumatology center who underwent WBMRI between January 2010 and December 2015 for the following indications: i) FUO (temperature greater than 38.3°C for more than three weeks or failure to reach diagnosis after one week of investigations), iii) recurrent fever (febrile episodes separated by periods of normal temperature), iii) Inflammation of unknown origin, IUO (an illness of at least 3 weeks’ duration, with raised inflammatory markers and fever below 38.3°C).WBMRI studies were acquired with coronal and sagittal planes (slice thickness 5mm) with acquisition of several image sets with automatic direct image realignment after acquisition creating a whole-body scan.Sequences include short τ inversion recovery (STIR) and T1-weighted. All studies have been evaluated twice, the second time according to a predefined checklist, defined by an experienced radiologist, considering systematically single /multifocal bone lesion, bone marrow, joint effusion, soft tissues, adenopathies, parenchymal and vessels looking for PDC. We considered as a Potential Diagnostic Clue each alteration of the examined district that can potentially guide the diagnosis. Each alteration found is a PDC. We retrospectively evaluated patients’ clinical history and final diagnosis and we classified the PDCs identified during both first evaluation and re-evaluation as: Not useful (the identified PDC did not guide the diagnosis and is not coherent with the final diagnosis), consistent (the identified PDC is congruent with the patient’s final diagnosis) or diagnostic (the identification of the considered PDC strongly orient the final diagnosis).Results:We collected 104 patients who underwent WBMRI; 24 (23%) of them presenting FUO, 28 (27%) presenting recurrent fever and 52 (50%) presenting IUO. The mean age of onset symptoms was 6 years and nine months (range: 2 weeks old- 17 years and 6 months). The mean age of execution of WBMRI was 9 years (range: 5 months old- 19 years). After the whole diagnostic work-out a final diagnosis was achieved in 44 patients (42%).PDCs were identified at the first evaluation in 78/104 cases (75%). In 22 cases (21%) the identified PDCs were consistent with the diagnosis, whereas in 9 cases (8.5%) the identified PDCs were considered diagnostic. Globally we can consider that at first evaluation PDCs were somehow contributory to the diagnosis in 31 cases (30%; 6 JIA, 7 systemic infections, 5 monogenic inflammatory diseases, 4 ALPS, 2 Goldbloom’s Syndrome,2 Vasculitis,1 eosinophilic fasciitis, 1 hystiocytosis, 3 oncologic diagnosis).Blind re-evaluation of WBMRI allowed the identification of additional PDCs in 52 patients (12 of them previously negative). In 10 cases the PDC found after re- evaluation were consistent with the final diagnosis (2 JIA, one infectious disease, one neuroblastoma, 3 ALPS, 1 monogenic inflammatory disease, 1Takayasu arteritis, 1 Goldbloom’s syndrome).Conclusion:WBMRI can be a powerful diagnostic tool in patients with FUO. A predefined checklist increases sensitivity of WBMRI in the identification of PDC.Disclosure of Interests:Sara Signa: None declared, Roberta Caorsi: None declared, Giorgio Stagnaro: None declared, Francesca Minoia: None declared, Paolo Picco: None declared, Angelo Ravelli: None declared, Maria Beatrice Damasio: None declared, Marco Gattorno Consultant of: Sobi, Novartis, Speakers bureau: Sobi, Novartis


2006 ◽  
Vol 399 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Sónia Troeira Henriques ◽  
Manuel Nuno Melo ◽  
Miguel A. R. B. Castanho

Some cationic peptides, referred to as CPPs (cell-penetrating peptides), have the ability to translocate across biological membranes in a non-disruptive way and to overcome the impermeable nature of the cell membrane. They have been successfully used for drug delivery into mammalian cells; however, there is no consensus about the mechanism of cellular uptake. Both endocytic and non-endocytic pathways are supported by experimental evidence. The observation that some AMPs (antimicrobial peptides) can enter host cells without damaging their cytoplasmic membrane, as well as kill pathogenic agents, has also attracted attention. The capacity to translocate across the cell membrane has been reported for some of these AMPs. Like CPPs, AMPs are short and cationic sequences with a high affinity for membranes. Similarities between CPPs and AMPs prompted us to question if these two classes of peptides really belong to unrelated families. In this Review, a critical comparison of the mechanisms that underlie cellular uptake is undertaken. A reflection and a new perspective about CPPs and AMPs are presented.


2002 ◽  
Vol 41 (01) ◽  
pp. 30-36 ◽  
Author(s):  
M. Heinisch ◽  
P. Mikosch ◽  
E. Kresnik ◽  
G. Kumnig ◽  
I. Gomez ◽  
...  

Summary Aim: Retrospective evaluation of Tc-99m ciprofloxacin (infecton) scintigraphy consecutively performed in a series of patients clinically suspected for peripheral osteomyelitis (OM), spondylodiscitis (SD) and fever of unknown origin (FUO). Methods: A total of 20 patients clinically suspected for OM (n = 12), SD (n = 3) and FUO (n = 5) were included in our retrospective analysis. The additional criterion was a positive 3-phase bone scan for OM, or a 2-phase bone scan in case of SD. Planar whole body scans and static acquisitions were performed 1 and 4 h after application of 370 MBq Tc-99m ciprofloxacin. In 10 patients with suspected OM, additional immunoscintigraphy using Tc-99m labelled monoclonal antibodies (Mab BW 250/183) was performed and the correlation of infecton to bloodpool and antigranulocyte scintigraphy was analysed. Results: OM: Bacterial infection was confirmed in 8 of 15 lesions. Infecton demonstrated true positive (TP) results in 7 of 8, true negative (TN) results in 2 of 7, false positive (FP) results in 5 of 7 patients and one false negative (FN) result. A strong correlation could be demonstrated between T/NT ratios of infecton and bloodpool Tc-99m medronate imaging (r = 0.84, 0.88) and between infecton and BW 250/183 (r = 0.92, 0.90). Using a threshold of 2.0 for T/NT ratio, only TP results could be observed whereas a T/NT in the range of 1.0-2.0 could not discriminate between septic and aseptic inflammation. Concordant results with Mab BW 250/183 could only be observed in 5 of 10 patients (4 TP, 1 TN) by showing 4 FP and 1 FN lesions with IF. Conclusion: Non-specific uptake of infecton can be observed in a variety of clinical situations with moderate uptake, by showing a strong correlation with blood-pool imaging. Nevertheless, intense uptake may be specific for septic inflammation.


2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Ryuji Komine ◽  
Takashi Kobayashi ◽  
Hiro Uehara ◽  
Keisuke Minamimura ◽  
Kazuhiko Mori ◽  
...  

Granulomatosis with polyangiitis (GPA) is known as anti-neutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis and typically manifests as pulmonary-renal syndrome, but the disease is not limited to pulmonary or renal systems. The inflammation can involve whole body organs. In addition, the ANCA titer does not always become positive. Here, we describe the case of a 91-year-old man who presented with umbilical pain and fever of unknown origin. Only the increased computed tomography value of the greater omentum suggested intra-abdominal inflammation; however, serological examinations, including the ANCA level, could not reveal the focus or cause of symptoms. Finally, the histopathological examination of specimens surgically excised from the greater omentum demonstrated GPA limited to the greater omentum. This report reminds physicians to consider GPA in the differential diagnosis of acute abdominal pain or fever of unknown origin.


2001 ◽  
Vol 40 (03) ◽  
pp. 59-70 ◽  
Author(s):  
W. Becker ◽  
J. Meiler

SummaryFever of unknown origin (FUO) in immunocompetent and non neutropenic patients is defined as recurrent fever of 38,3° C or greater, lasting 2-3 weeks or longer, and undiagnosed after 1 week of appropriate evaluation. The underlying diseases of FUO are numerous and infection accounts for only 20-40% of them. The majority of FUO-patients have autoimmunity and collagen vascular disease and neoplasm, which are responsible for about 50-60% of all cases. In this respect FOU in its classical definition is clearly separated from postoperative and neutropenic fever where inflammation and infection are more common. Although methods that use in-vitro or in-vivo labeled white blood cells (WBCs) have a high diagnostic accuracy in the detection and exclusion of granulocytic pathology, they are only of limited value in FUO-patients in establishing the final diagnosis due to the low prevalence of purulent processes in this collective. WBCs are more suited in evaluation of the focus in occult sepsis. Ga-67 citrate is the only commercially available gamma emitter which images acute, chronic, granulomatous and autoimmune inflammation and also various malignant diseases. Therefore Ga-67 citrate is currently considered to be the tracer of choice in the diagnostic work-up of FUO. The number of Ga-67-scans contributing to the final diagnosis was found to be higher outside Germany than it has been reported for labeled WBCs. F-l 8-2’-deoxy-2-fluoro-D-glucose (FDG) has been used extensively for tumor imaging with PET. Inflammatory processes accumulate the tracer by similar mechanisms. First results of FDG imaging demonstrated, that FDG may be superior to other nuclear medicine imaging modalities which may be explained by the preferable tracer kinetics of the small F-l 8-FDG molecule and by a better spatial resolution of coincidence imaging in comparison to a conventional gamma camera.


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