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Catharina M. L. Zegers Wouter van Elmpt Katrin Szardenings Hartmuth Kolb Alan Waxman Rathan M. Subramaniam Dae Hyuk Moon Jacqueline C. Brunetti Shyam M. Srinivas Philippe Lambin David Chien 《European journal of nuclear medicine and molecular imaging》2015,42(12):1840-1849
Purpose
Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [18F]HX4 in patients with head and neck and lung cancer.Methods
Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [18F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.Results
All parameters of [18F]HX4 uptake were significantly correlated between scans: SUVmax (r?=?0.958, p?<?0.001), SUVmean (r?=?0.946, p?<?0.001), TBRmax (r?=?0.962, p?<?0.001) and HV1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.Conclusion
Repeated hypoxia PET scans with [18F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [18F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.104.
Ulf C. Schneider Katrin Bohlmann Peter Vajkoczy Hans-Beatus Straub 《Acta neurochirurgica》2015,157(4):721-728
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Miriam Puls Claudia Dellas Mareike Lankeit Manfred Olschewski Lutz Binder Anette Geibel Christian Reiner Katrin Sch?fer Gerd Hasenfuss Stavros Konstantinides 《European heart journal》2007,28(2):224-229
AIMS: We investigated the value of a novel early biomarker, heart-type fatty acid-binding protein (H-FABP), in risk stratification of patients with acute pulmonary embolism (PE). METHODS AND RESULTS: We prospectively included 107 consecutive patients with confirmed PE. The endpoints were (i) PE-related death or major complications and (ii) overall 30-day mortality. Overall, 29 patients (27%) had abnormal (>6 ng/mL) H-FABP levels at presentation. Of those, 12 (41%) had a complicated course, whereas all patients with normal baseline H-FABP had a favourable 30-day outcome (OR, 71.45; P<0.0001). At multivariable analysis, H-FABP (P<0.0001), but not cardiac troponin T (P=0.13) or N-terminal pro-brain natriuretic peptide (P=0.36), predicted an adverse outcome. Evaluation of a strategy combining biomarker testing with echocardiography revealed that patients with a negative H-FABP test had an excellent prognosis regardless of echocardiographic findings. In contrast, patients with a positive H-FABP test had a complication rate of 23.1% even in the presence of a normal echocardiogram, and this rose to 57.1% if echocardiography also demonstrated right ventricular dysfunction (OR vs. a negative H-FABP test, 5.6 and 81.4, respectively). CONCLUSION: H-FABP is a promising early indicator of right ventricular injury and dysfunction in acute PE. It may help optimize risk stratification algorithms and treatment strategies. 相似文献
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Daniela Münch Ina Engels Anna Müller Katrin Reder-Christ Hildegard Falkenstein-Paul Gabriele Bierbaum Fabian Grein Gerd Bendas Hans-Georg Sahl Tanja Schneider 《Antimicrobial agents and chemotherapy》2015,59(2):772-781
Oritavancin is a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin with activity against Gram-positive pathogens, including vancomycin-resistant staphylococci and enterococci. Compared to vancomycin, oritavancin is characterized by the presence of two additional residues, a hydrophobic 4′-chlorobiphenyl methyl moiety and a 4-epi-vancosamine substituent, which is also present in chloroeremomycin. Here, we show that oritavancin and its des-N-methylleucyl variant (des-oritavancin) effectively inhibit lipid I- and lipid II-consuming peptidoglycan biosynthesis reactions in vitro. In contrast to that for vancomycin, the binding affinity of oritavancin to the cell wall precursor lipid II appears to involve, in addition to the d-Ala-d-Ala terminus, other species-specific binding sites of the lipid II molecule, i.e., the crossbridge and d-isoglutamine in position 2 of the lipid II stem peptide, both characteristic for a number of Gram-positive pathogens, including staphylococci and enterococci. Using purified lipid II and modified lipid II variants, we studied the impact of these modifications on the binding of oritavancin and compared it to those of vancomycin, chloroeremomycin, and des-oritavancin. Analysis of the binding parameters revealed that additional intramolecular interactions of oritavancin with the peptidoglycan precursor appear to compensate for the loss of a crucial hydrogen bond in vancomycin-resistant strains, resulting in enhanced binding affinity. Augmenting previous findings, we show that amidation of the lipid II stem peptide predominantly accounts for the increased binding of oritavancin to the modified intermediates ending in d-Ala-d-Lac. Corroborating our conclusions, we further provide biochemical evidence for the phenomenon of the antagonistic effects of mecA and vanA resistance determinants in Staphylococcus aureus, thus partially explaining the low frequency of methicillin-resistant S. aureus (MRSA) acquiring high-level vancomycin resistance. 相似文献
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