Purpose
We aimed to determine the test–retest repeatability of quantitative metrics based on the Patlak slope (PS) versus the standardized uptake value (SUV) among lesions and normal organs on ...oncologic
18
FFDG-PET/CT.
Procedures
This prospective, single-center study enrolled adults undergoing standard-of-care oncologic
18
FFDG-PET/CTs. Early (35–50 min post-injection) and late (75–90 min post-injection) SUV and PS images were reconstructed from dynamic whole-body PET data. Repeat imaging occurred within 7 days. Relevant quantitative metrics were extracted from lesions and normal organs. Repeatability was assessed via mean test–retest percent changes T-RT %Δ, within-subject coefficients of variation (wCVs), and intra-class correlation coefficients (ICCs).
Results
Nine subjects (mean age, 61.7 ± 6.2 years; 6 females) completed the test–retest protocol. Four subjects collectively had 17
18
FFDG-avid lesions. Lesion wCVs were higher (i.e., worse repeatability) for PS-early-max (16.2%) and PS-early-peak (15.6%) than for SUV-early-max (8.9%) and SUV-early-peak (8.1%), with similar early metric ICCs (0.95–0.98). Lesion wCVs were similar for PS-late-max (8.5%) and PS-late-peak (6.4%) relative to SUV-late-max (9.7%) and SUV-late-peak (7.2%), with similar late metric ICCs (0.93–0.98). There was a significant bias toward higher retest SUV and PS values in the lesion analysis (T-RT %Δ 95% CI: SUV-late-max, 10.0% 2.6%, 17.0%; PS-late-max, 20.4% 14.3%, 26.4%) but not in the normal organ analysis.
Conclusions
Among
18
FFDG-avid lesions, the repeatability of PS-based metrics is similar to equivalent SUV-based metrics at late post-injection time points, indicating that PS-based metrics may be suitable for tracking response to oncologic therapies. However, further validation is required in light of our study’s limitations, including small sample size and bias toward higher retest values for some metrics.
Guanylate binding proteins (GBPs) are soluble dynamin-like proteins that undergo a conformational transition for GTP-controlled oligomerization and disrupt membranes of intracellular parasites to ...exert their function as part of the innate immune system of mammalian cells. We apply neutron spin echo, X-ray scattering, fluorescence, and EPR spectroscopy as techniques for integrative dynamic structural biology to study the structural basis and mechanism of conformational transitions in the human GBP1 (hGBP1). We mapped hGBP1's essential dynamics from nanoseconds to milliseconds by motional spectra of sub-domains. We find a GTP-independent flexibility of the C-terminal effector domain in the µs-regime and resolve structures of two distinct conformers essential for an opening of hGBP1 like a pocket knife and for oligomerization. Our results on hGBP1's conformational heterogeneity and dynamics (intrinsic flexibility) deepen our molecular understanding relevant for its reversible oligomerization, GTP-triggered association of the GTPase-domains and assembly-dependent GTP-hydrolysis.
To date, many major radiation accidents have occurred worldwide, mostly in nuclear reactors, and some other minors in radioactive isotope production facilities and during the transport of radioactive ...materials. Similarly, the majority of the radiation accidents in Turkey occurred in industrial radiology or during the use of sealed radioactive sources for the purpose of nondestructive testing. However, only a few of them happened in medical practices. In case of fire in buildings with radioactive material, terrorist incidents using radioactive materials, or accidents during transportation of radioactive materials, emergency response teams, first aiders and firefighters may be exposed to low-level radiation while performing their duties. Fortunately, very few victims of radiation accidents develop acute radiation syndrome and require medical intervention. On the other hand, some victims of radionuclear accidents may require urgent medical intervention since the adverse health effects may occur years after the event due to internal contamination and following incorporation. In this report, we aimed to define the basic concepts of radionuclear emergency and medical management of radionuclear victims. Keywords: Radionuclear emergency, acute radiation syndrome, medical management
Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the ...guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction. Using vesicles of various sizes as a lipid bilayer model, we show GTP-dependent membrane binding of hGBP1F. In addition, we demonstrate nucleotide-dependent tethering ability of hGBP1F. Furthermore, we report nucleotide-dependent polymerization of hGBP1F, which competes with membrane binding of the protein. Our results show that hGBP1F acts as a nucleotide-controlled molecular switch by modulating the accessibility of its farnesyl moiety, which does not require any supportive proteins.
Fever of unknown origin (FUO) is defined as an illness having fever which lasts at least 3 weeks of duration and is higher than 38.3 ºC on several measurements. The causes are infections, ...malignancies, noninfectious inflammatory diseases and miscellaneous. If 18FFDG-PET/CT helps the final diagnosis, it is called contributory. The aim of the study is to evaluate the predictor variables effecting a contributory PET/CT for the diagnosis.
This is a retrospective cohort study conducted between June 2006 and May 2015 including 76 patients. The evaluated predictor variables are age, sex, ESR, CRP, fibrinogen, ferritin, albumin, haemoglobin level, platelet count, total leukocyte count, neutrophil percentage, lymphocyte percentage, ALP, LDH, ALAT, ASAT, GGT, total bilirubin, CK, RF, ANA, urinanalysis, chest radiography, abdominal US, lymphadenopathy, duration of fever, comorbid diseases and previous therapies.
ESR (P=0.001), CRP (P=0.001), fibrinogen (P=0.009), lymphopenia (P<0.001), neutrophilia (P<0.001), ferritin (P<0.001), leukocytosis (P=0.003), duration of fever before PET/CT (<3 months) were found to be statistically significant for positive contribution of PET/CT results to the diagnosis. CONCLUSİONS: 18FFDG-PET/CT is helpful and contributory for the diagnosis of FUO in patients having higher levels of CRP, ESR, ferritin, fibrinogen, leukocytosis, neutrophilia and shorter durations of fever (<3 months).
ATP-binding and hydrolysis of human NLRP3 Brinkschulte, Rebecca; Fußhöller, David M; Hoss, Florian ...
Communications biology,
11/2022, Letnik:
5, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The innate immune system uses inflammasomal proteins to recognize danger signals and fight invading pathogens. NLRP3, a multidomain protein belonging to the family of STAND ATPases, is characterized ...by its central nucleotide-binding NACHT domain. The incorporation of ATP is thought to correlate with large conformational changes in NLRP3, leading to an active state of the sensory protein. Here we analyze the intrinsic ATP hydrolysis activity of recombinant NLRP3 by reverse phase HPLC. Wild-type NLRP3 appears in two different conformational states that exhibit an approximately fourteen-fold different hydrolysis activity in accordance with an inactive, autoinhibited state and an open, active state. The impact of canonical residues in the nucleotide binding site as the Walker A and B motifs and sensor 1 and 2 is analyzed by site directed mutagenesis. Cellular experiments show that reduced NLRP3 hydrolysis activity correlates with higher ASC specking after inflammation stimulation. Addition of the kinase NEK7 does not change the hydrolysis activity of NLRP3. Our data provide a comprehensive view on the function of conserved residues in the nucleotide-binding site of NLRP3 and the correlation of ATP hydrolysis with inflammasome activity.
Patlak slope (PS) images have the potential to improve lesion conspicuity compared with standardized uptake value (SUV) images but may be more artifact-prone. This study compared PS versus SUV image ...quality and hepatic tumor-to-background ratios (TBRs) at matched time points. Early and late SUV and PS images were reconstructed from dynamic positron emission tomography (PET) data. Two independent, blinded readers scored image quality metrics (a four-point Likert scale) and counted tracer-avid lesions. Hepatic lesions and parenchyma were segmented and quantitatively analyzed. Differences were assessed via the Wilcoxon signed-rank test (alpha, 0.05). Forty-three subjects were included. For overall quality and lesion detection, early PS images were significantly inferior to other reconstructions. For overall quality, late PS images (reader 1 R1: 3.95, reader 2 R2: 3.95) were similar (
> 0.05) to early SUV images (R1: 3.88, R2: 3.84) but slightly superior (
≤ 0.002) to late SUV images (R1: 2.97, R2: 3.44). For lesion detection, late PS images were slightly inferior to late SUV images (R1 only) but slightly superior to early SUV images (both readers). PS-based TBRs were significantly higher than SUV-based TBRs at the early time point, with opposite findings at the late time point. In conclusion, late PS images are similar to early/late SUV images in image quality and lesion detection; the superiority of SUV versus PS hepatic TBRs is time-dependent.
Introduction. Differentiation between a malignancy and inflammatory process is still a diagnostic challenge. Mammography (MG) and ultrasonography (US) have low sensitivity and specificity in dense ...breasts in order to detect malignancy. On the other hand, malignant mass lesions can also be masked on magnetic resonance imaging (MRI) by diffuse inflammatory process. 18-fluorodeoxyglucose positron emission tomography (FDG PET) imaging can be a promising alternative imaging method in the evaluation of suspicious breast masses, especially in patients with accompanying inflammatory breast diseases. Case report. We report an atypical case of a patient suspected for malignancy in right breast on physical examination and radiologic findings in favor of mastitis. Neither MG nor US revealed any mass lesion consistent with malignancy. Moreover, MRI findings were primarily considered as infectious or granulomatous mastitis. However, FDG PET determined the accurate borders of tumor and dissemination of breast cancer with superiority to other conventional radiological methods. Conclusion. This case report emphasizes the contribution of FDG PET imaging to other conventional radiological methods with regard to primary tumor diagnosis, determination of the biopsy site, and also staging the disease especially in patients with accompanying inflammatory breast disease.
nema
Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (
F-FDG) positron emission tomography/computed tomography ...(PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of
F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC.
We examined the SUVmax value of lesions on control or restaging
F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax values were confirmed by colonoscopy or histopathology. We compared PET/CT results with conventional imaging modalities (CT, MRI) and tumor markers (carbohydrate antigen 19-9 Ca 19-9, carcinoembryonic antigen CEA).
Mean SUVmax was 6.9 ± 5.6 in benign group, 12.7 ± 6.1 in malignant group. Mean TLG values of malignant group and benign group were 401 and 148, respectively.
F-FDG-PET/CT was truely positive in 48% of patients with normal Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9 or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and
F-FDG-PET/CT was truely negative in 35% of these cases. We found the most important and striking statistical difference of TLG value between the groups with benign and recurrent disease.
Although SUVmax is a strong metabolic parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p = 0.001); both are increasing the specificity of
F-FDG-PET/CT.
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