A kit-based aluminium-[18F]fluoride approach to radiolabelled microbubbles.
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ABSTRACT:
SUBMITTER: Teh JH
PROVIDER: S-EPMC8567295 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Photosynthesis uses chlorophylls for the conversion of light into chemical energy, the driving force of life on Earth. During chlorophyll biosynthesis in photosynthetic bacteria, cyanobacteria, green algae and gymnosperms, dark-operative protochlorophyllide oxidoreductase (DPOR), a nitrogenase-like metalloenzyme, catalyzes the chemically challenging two-electron reduction of the fully conjugated ring system of protochlorophyllide a. The reduction of the C-17=C-18 double bond results in the characteristic ring architecture of all chlorophylls, thereby altering the absorption properties of the molecule and providing the basis for light-capturing and energy-transduction processes of photosynthesis. We report the X-ray crystallographic structure of the substrate-bound, ADP-aluminium fluoride-stabilized (ADP·AlF(3)-stabilized) transition state complex between the DPOR components L(2) and (NB)(2) from the marine cyanobacterium Prochlorococcus marinus. Our analysis permits a thorough investigation of the dynamic interplay between L(2) and (NB)(2). Upon complex formation, substantial ATP-dependent conformational rearrangements of L(2) trigger the protein-protein interactions with (NB)(2) as well as the electron transduction via redox-active [4Fe-4S] clusters. We also present the identification of artificial "small-molecule substrates" of DPOR in correlation with those of nitrogenase. The catalytic differences and similarities between DPOR and nitrogenase have broad implications for the energy transduction mechanism of related multiprotein complexes that are involved in the reduction of chemically stable double and/or triple bonds.
| S-EPMC3568340 | biostudies-literature
Project description:The evidence on atherosclerosis imaging with 18F-sodium-fluoride (NaF) positron emission tomography (PET) is hotly debated because of the different patient characteristics, methodology, vascular beds, etc. in reported studies. This review is a continuation of a previous review on this topic, which covered the period 2010-2018. The purpose was to examine whether some of the most important questions that the previous review had left open had been elucidated by the most recent literature. Using principles of a systematic review, we ended analyzing 25 articles dealing with the carotids, coronary arteries, aorta, femoral, intracranial, renal, and penile arteries. The knowledge thus far can be summarized as follows: by targeting active arterial microcalcification, NaF uptake is considered a marker of early stage atherosclerosis, is age-dependent, and consistently associated with cardiovascular risk. Longitudinal studies on NaF uptake, conducted in the abdominal aorta only, showed unchanged uptake in postmenopausal women for nearly four years and varying uptake in prostate cancer patients over 1.5 years, despite constant or increasing calcium volume detected by computed tomography (CT). Thus, uncertainty remains about the transition from active arterial wall calcification marked by increased NaF uptake to less active or consolidated calcification detected by CT. The question of whether early-phase atherosclerosis and calcification can be modified remains also unanswered due to lack of intervention studies.
| S-EPMC7590213 | biostudies-literature
Project description:A one-step oxidative fluorination for carbon-fluorine bond formation from well-defined nickel complexes with oxidant and aqueous fluoride is presented, which enables a straightforward and practical (18)F late-stage fluorination of complex small molecules with potential for PET imaging.
| S-EPMC3494465 | biostudies-literature
Project description:Atherosclerosis is the leading cause of life-threatening morbidity and mortality, as the rupture of atherosclerotic plaques leads to critical atherothrombotic events such as myocardial infarction and ischemic stroke, which are the 2 most common causes of death worldwide. Vascular calcification is a complicated pathological process involved in atherosclerosis, and microcalcifications are presumed to increase the likelihood of plaque rupture. Despite many efforts to develop novel non-invasive diagnostic modalities, diagnostic techniques are still limited, especially before symptomatic presentation. From this point of view, vulnerable plaques are a direct target of atherosclerosis imaging. Anatomic imaging modalities have the limitation of only visualizing macroscopic structural changes, which occurs in later stages of disease, while molecular imaging modalities are able to detect microscopic processes and microcalcifications, which occur early in the disease process. Na[18F]-fluoride positron emission tomography/computed tomography could allow the early detection of plaque instability, which is deemed to be a primary goal in the prevention of cardiac or brain ischemic events, by quantifying the microcalcifications within vulnerable plaques and evaluating the atherosclerotic disease burden.
| S-EPMC7521973 | biostudies-literature
Project description:BackgroundChallenges to cardiac PET-CT include patient motion, prolonged image acquisition and a reduction of counts due to gating. We compared two analytical tools, FusionQuant and OsiriX, for quantification of gated cardiac 18F-sodium fluoride (18F-fluoride) PET-CT imaging.MethodsTwenty-seven patients with aortic stenosis were included, 15 of whom underwent repeated imaging 4 weeks apart. Agreement between analytical tools and scan-rescan reproducibility was determined using the Bland-Altman method and Lin's concordance correlation coefficients (CCC).ResultsImage analysis was faster with FusionQuant [median time (IQR) 7:10 (6:40-8:20) minutes] compared with OsiriX [8:30 (8:00-10:10) minutes, p = .002]. Agreement of uptake measurements between programs was excellent, CCC = 0.972 (95% CI 0.949-0.995) for mean tissue-to-background ratio (TBRmean) and 0.981 (95% CI 0.965-0.997) for maximum tissue-to-background ratio (TBRmax). Mean noise decreased from 11.7% in the diastolic gate to 6.7% in motion-corrected images (p = .002); SNR increased from 25.41 to 41.13 (p = .0001). Aortic valve scan-rescan reproducibility for TBRmax was improved with FusionQuant using motion correction compared to OsiriX (error ± 36% vs ± 13%, p < .001) while reproducibility for TBRmean was similar (± 10% vs ± 8% p = .252).Conclusion18F-fluoride PET quantification with FusionQuant and OsiriX is comparable. FusionQuant with motion correction offers advantages with respect to analysis time and reproducibility of TBRmax values.
| S-EPMC6541558 | biostudies-literature
Project description:BackgroundPositron emission tomography using the [18F] fluoride metabolite combined with computerized tomography (F-PET/CT) can be used to analyze the metabolic status of the periprosthetic bone after surgery for total hip arthroplasty.MethodsTo obtain normal PET referent values, 44 patients with 5 models of well-functioning hip prosthetic components were analyzed by F-PET/CT, radiography, and clinical score. Another group of patients having painful total hip arthroplasty, but whose radiography showed no conclusive signs of loosening, was analyzed by F-PET/CT scans before revision surgery.ResultsPreoperative median F-PET scores of the bone metabolic activity were 6.65 (3.3-9.0) for the painful stem group and 1.85 (1.2-3.9) (P < .01) for the referent group having the same stem model. At revision surgery, the stems in the painful group were assessed to be loose. At 2-year follow-up, the revised patients were all pain free.ConclusionF-PET/CT may be a new diagnostic tool for assessing occult loose stems that are not seen by radiography.
| S-EPMC7397393 | biostudies-literature
Project description:Mechanochemical proteins rely on ATP hydrolysis to establish the different functional states required for their biological output. Studying the transient functional intermediate states these proteins adopt as they progress through the ATP hydrolysis cycle is key to understanding the molecular basis of their mechanism. Many of these intermediates have been successfully 'trapped' and functionally characterised using ATP analogues. Here, we present a new nucleotide analogue, AMP-AlF(x), which traps PspF, a bacterial enhancer binding protein, in a stable complex with the sigma(54)-RNA polymerase holoenzyme. The crystal structure of AMP-AlF(x)*PspF(1-275) provides new information on protein-nucleotide interactions and suggests that the beta and gamma phosphates are more important than the alpha phosphate in terms of sensing nucleotide bound states. In addition, functional data obtained with AMP-AlF(x) establish distinct roles for the conserved catalytic AAA(+) (ATPases associated with various cellular activities) residues, suggesting that AMP-AlF(x) is a powerful new tool to study AAA(+) protein family members and, more generally, Walker motif ATPases.
| S-EPMC2776300 | biostudies-literature
Project description:BACKGROUND:Oncrasin-1 is a small molecule which was identified from a screen of KRAS mutant cancer cells and has shown specificity for KRAS mutant cell killing. We aimed to develop a radiolabelled form of Oncrasin-1 to enable in-vivo imaging of mutant KRAS expression in malignant tumours. This work outlines the synthesis of 3 fluorinated derivatives and development of iodonium salt and boronic ester precursors for radiolabelling with the 18F isotope. RESULTS:In our hands, synthesis of iodonium salts were not easily accessible due to the 3-carbaldehyde indole structure being preferentially oxidized by conditions required for iodonium salt formation, rather than benzyl iodide. Synthesis and radiolabelling of boronic acid pinacol ester precursors were successful, with the products being obtained in yields of 10.76%?±?0.96% (n?=?5), 14.7% ±8.58% (n?=?3) and 14.92% ±3.9% (n?=?3) for 18F KAM001, 18F KAM002 and 18F KAM003 respectively, with radiochemical purity of greater than 99%. CONCLUSIONS:The successful synthesis of these tracers has been undertaken utilizing boronic ester radio-fluorination methods and will allow for investigation of Oncrasin based molecules as potential diagnostics for cancers expressing mutant KRAS protein.
| S-EPMC7652984 | biostudies-literature
Project description:PURPOSE:We examined the literature to elucidate the role of 18F-sodium fluoride (NaF)-PET in atherosclerosis. METHODS:Following a systematic search of PubMed/MEDLINE, Embase, and Cochrane Library included articles underwent subjective quality assessment with categories low, medium, and high. Of 2811 records, 1780 remained after removal of duplicates. Screening by title and abstract left 41 potentially eligible full-text articles, of which 8 (about the aortic valve (n = 1), PET/MRI feasibility (n = 1), aortic aneurysms (n = 1), or quantification methodology (n = 5)) were dismissed, leaving 33 published 2010-2012 (n = 6), 2013-2015 (n = 11), and 2016-2018 (n = 16) for analysis. RESULTS:They focused on coronary (n = 8), carotid (n = 7), and femoral arteries (n = 1), thoracic aorta (n = 1), and infrarenal aorta (n = 1). The remaining 15 studies examined more than one arterial segment. The literature was heterogeneous: few studies were designed to investigate atherosclerosis, 13 were retrospective, 9 applied both FDG and NaF as tracers, 24 NaF only. Subjective quality was low in one, medium in 13, and high in 19 studies. The literature indicates that NaF is a very specific tracer that mimics active arterial wall microcalcification, which is positively associated with cardiovascular risk. Arterial NaF uptake often presents before CT-calcification, tends to decrease with increasing density of CT-calcification, and appears, rather than FDG-avid foci, to progress to CT-calcification. It is mainly surface localized, increases with age with a wide scatter but without an obvious sex difference. NaF-avid microcalcification can occur in fatty streaks, but the degree of progression to CT-calcification is unknown. It remains unknown whether medical therapy influences microcalcification. The literature held no therapeutic or randomized controlled trials. CONCLUSION:The literature was heterogeneous and with few clear cut messages. NaF-PET is a new approach to detect and quantify microcalcification in early-stage atherosclerosis. NaF uptake correlates with cardiovascular risk factors and appears to be a good measure of the body's atherosclerotic burden, potentially suited also for assessment of anti-atherosclerotic therapy.
| S-EPMC7188711 | biostudies-literature
Project description:BackgroundWe aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA).MethodsPatients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level.ResultsIn 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary18F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively.ConclusionsCMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.
| S-EPMC7728624 | biostudies-literature