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Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis.
de Zwart, PL, van Dijken, BRJ, Holtman, GA, Stormezand, GN, Dierckx, RAJO, Jan van Laar, P, van der Hoorn, A
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020;(4):498-504
Abstract
Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%-100%, respectively, for 18F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%-88%, respectively, for 11C-choline. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.
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18F-Sodium Fluoride PET: History, Technical Feasibility, Mechanism of Action, Normal Biodistribution, and Diagnostic Performance in Bone Metastasis Detection Compared with Other Imaging Modalities.
Ahuja, K, Sotoudeh, H, Galgano, SJ, Singh, R, Gupta, N, Gaddamanugu, S, Choudhary, G
Journal of nuclear medicine technology. 2020;(1):9-16
Abstract
The skeleton is the third most common site for metastasis overall, after the lungs and liver. Accurate diagnosis of osseous metastasis is critical for initial staging, treatment planning, restaging, treatment monitoring, and survival prediction. Currently, 99mTc-methylene diphosphonate whole-body scanning is the cornerstone of imaging to detect osseous metastasis. Although 18F-sodium fluoride (18F-NaF) was one of the oldest medical tracers for this purpose, it was replaced by other tracers because of their better physical properties, until recently. Continued development of PET scanners has opened a new era for 18F-NaF, and given its higher sensitivity, there have been increasing applications in imaging. In this review, we will discuss the history, technical aspects, radiobiology, and biodistribution of this tracer. Finally, we compare the accuracy of 18F-NaF PET with other conventional imaging methods for detection of osseous metastasis.
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Phase-III Clinical Trial of Fluorine-18 Flurpiridaz Positron Emission Tomography for Evaluation of Coronary Artery Disease.
Maddahi, J, Lazewatsky, J, Udelson, JE, Berman, DS, Beanlands, RSB, Heller, GV, Bateman, TM, Knuuti, J, Orlandi, C
Journal of the American College of Cardiology. 2020;(4):391-401
Abstract
BACKGROUND Fluorine-18 flurpiridaz is a novel positron emission tomography (PET) myocardial perfusion imaging tracer. OBJECTIVES This study sought to assess the diagnostic efficacy of flurpiridaz PET versus technetium-99m-labeled single photon emission computed tomography SPECT for the detection and evaluation of coronary artery disease (CAD), defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA). Flurpiridaz safety was also evaluated. METHODS In this phase III prospective multicenter clinical study, 795 patients with known or suspected CAD from 72 clinical sites in the United States, Canada, and Finland were enrolled. A total of 755 patients were evaluable, and the mean age was 62.3 ± 9.5 years, 31% were women, 55% had body mass index ≥30 kg/m2, and 71% had pharmacological stress. Patients underwent 1-day rest-stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled SPECT and ICA. Images were read by 3 experts blinded to clinical and ICA data. RESULTS Sensitivity of flurpiridaz PET (for detection of ≥50% stenosis by ICA) was 71.9% (95% confidence interval [CI]: 67.0% to 76.3%), significantly (p < 0.001) higher than SPECT (53.7% [95% CI: 48.5% to 58.8%]), while specificity did not meet the prespecified noninferiority criterion (76.2% [95% CI: 71.8% to 80.1%] vs. 86.6% [95% CI: 83.2% to 89.8%]; p = NS). Receiver-operating characteristic curve analysis demonstrated superior discrimination of CAD by flurpiridaz PET versus SPECT in the overall population, in women, obese patients, and patients undergoing pharmacological stress testing (p < 0.001 for all). Flurpiridaz PET was superior to SPECT for defect size (p < 0.001), image quality (p < 0.001), diagnostic certainty (p < 0.001), and radiation exposure (6.1 ± 0.4 mSv vs. 13.4 ± 3.2 mSv; p < 0.001). Flurpiridaz PET was safe and well tolerated. CONCLUSIONS Flurpiridaz PET myocardial perfusion imaging shows promise as a new tracer for CAD detection and assessment of women, obese patients, and patients undergoing pharmacological stress testing. A second phase III Food and Drug Administration trial is ongoing. (A Phase 3 Multi-center Study to Assess PET Imaging of Flurpiridaz F 18 Injection in Patients with CAD; NCT01347710).
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Aortic valve stenosis-multimodality assessment with PET/CT and PET/MRI.
Tzolos, E, Andrews, JP, Dweck, MR
The British journal of radiology. 2020;(1113):20190688
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Abstract
Aortic valve disease is the most common form of heart valve disease in developed countries and a growing healthcare burden with an ageing population. Transthoracic and transoesophageal echocardiography remains central to the diagnosis and surveillance of patients with aortic stenosis, providing gold standard assessments of valve haemodynamics and myocardial performance. However, other multimodality imaging techniques are being explored for the assessment of aortic stenosis, including combined PET/CT and PET/MR. Both approaches provide unique information with respect to disease activity in the valve alongside more conventional anatomic assessments of the valve and myocardium in this condition. This review investigates the emerging use of PET/CT and PET/MR to assess patients with aortic stenosis, examining how the complementary data provided by each modality may be used for research applications and potentially in future clinical practice.
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Cardiac Imaging With 123I-meta-iodobenzylguanidine and Analogous PET Tracers: Current Status and Future Perspectives.
Wan, N, Travin, MI
Seminars in nuclear medicine. 2020;(4):331-348
Abstract
Autonomic innervation plays an important role in proper functioning of the cardiovascular system. Altered cardiac sympathetic function is present in a variety of diseases, and can be assessed with radionuclide imaging using sympathetic neurotransmitter analogues. The most studied adrenergic radiotracer is cardiac 123I-meta-iodobenzylguanidine (123I-mIBG). Cardiac 123I-mIBG uptake can be evaluated using both planar and tomographic imaging, thereby providing insight into global and regional sympathetic innervation. Standardly assessed imaging parameters are the heart-to-mediastinum ratio and washout rate, customarily derived from planar images. Focal tracer deficits on tomographic imaging also show prognostic utility, with some data suggesting that the best approach to tomographic image interpretation may differ from conventional methods. Cardiac 123I-mIBG image findings strongly correlate with the severity and prognosis of many cardiovascular diseases, especially heart failure and ventricular arrhythmias. Cardiac 123I-mIBG imaging in heart failure is FDA approved for prognostic purposes. With the robustly demonstrated ability to predict occurrence of potentially fatal arrhythmias, cardiac 123I-mIBG imaging shows promise for better selecting patients who will benefit from an implantable cardioverter defibrillator, but clinical use has been hampered by lack of the randomized trial needed for incorporation into societal guidelines. In patients with ischemic heart disease, cardiac 123I-mIBG imaging aids in assessing the extent of damage and in identifying arrhythmogenic regions. There have also been studies using cardiac 123I-mIBG for other conditions, including patients following heart transplantation, diabetic related cardiac abnormalities and chemotherapy induced cardiotoxicity. Positron emission tomographic adrenergic radiotracers, that improve image quality, have been investigated, especially 11C-meta-hydroxyephedrine, and most recently 18F-fluorbenguan. Cadmium-zinc-telluride cameras also improve image quality. With better spatial resolution and quantification, PET tracers and advanced camera technologies promise to expand the clinical utility of cardiac sympathetic imaging.
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Molecular Imaging in the Head and Neck: Diagnosis and Therapy.
Howard, BA
Radiologic clinics of North America. 2020;(6):1135-1146
Abstract
This article is a summary of the most up-to-date applications of radiopharmaceuticals to the diagnosis and therapy of benign and malignant diseases involving endocrine or neuroendocrine organs of the head and neck, focusing on radiotracers approved by the US Food and Drug Administration, such as I-123- and I-131-sodium iodide, F-18-fluorodeoxyglucose, Tc99m-sestamibi, as well as the more recently approved tracers Ga-68 DOTATATE and Lu-177 DOTATATE.
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An Update on the Role of Total-Body PET Imaging in the Evaluation of Atherosclerosis.
Borja, AJ, Rojulpote, C, Hancin, EC, Høilund-Carlsen, PF, Alavi, A
PET clinics. 2020;(4):477-485
Abstract
Fused PET/computed tomography has demonstrated success in the detection and quantification of atherosclerotic plaques. Recently, total-body PET imaging has demonstrated increased sensitivity and specificity in atherosclerosis. This article reviews the literature regarding this novel imaging technique. Moreover, evidence that has pointed toward 18F-sodium fluoride as the radiotracer of choice over 18F-fluorodeoxyglucose for evaluation of plaque burden is discussed. Finally, a global disease assessment is introduced as an adjunct tool for vascular PET imaging.
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Positron Emission Particle Tracking of Granular Flows.
Windows-Yule, CRK, Seville, JPK, Ingram, A, Parker, DJ
Annual review of chemical and biomolecular engineering. 2020;:367-396
Abstract
Positron emission particle tracking (PEPT) is a noninvasive technique capable of imaging the three-dimensional dynamics of a wide variety of powders, particles, grains, and/or fluids. The PEPT technique can track the motion of particles with high temporal and spatial resolution and can be used to study various phenomena in systems spanning a broad range of scales, geometries, and physical states. We provide an introduction to the PEPT technique, an overview of its fundamental principles and operation, and a brief review of its application to a diverse range of scientific and industrial systems.
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Comparison of 18F-FDG PET-MR and fecal biomarkers in the assessment of disease activity in patients with ulcerative colitis.
Li, Y, Khamou, M, Schaarschmidt, BM, Umutlu, L, Forsting, M, Demircioglu, A, Haubold, J, Koch, AK, Bruckmann, NM, Sawicki, LM, et al
The British journal of radiology. 2020;(1112):20200167
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Abstract
OBJECTIVE To compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis. METHODS This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated. RESULTS According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05). CONCLUSION Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis. ADVANCES IN KNOWLEDGE Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.
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Comparison of gallium-68 somatostatin receptor and 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of neuroendocrine tumours: A systematic review and meta-analysis.
Liu, X, Li, N, Jiang, T, Xu, H, Ran, Q, Shu, Z, Wu, J, Li, Y, Zhou, S, Zhang, B
Hellenic journal of nuclear medicine. 2020;(2):188-200
Abstract
OBJECTIVE A meta-analysis was performed to compare the diagnostic performance of gallium-68 (18Ga) somatostatin receptor positron emission tomography (68Ga-SSTR PET) and fluorine-18-fluorodeoxyglucose (18F-FDG) PET in patients with neuroendocrine tumours (NET) and whether the two imaging modalities can be mutually substituted in clinical work. METHODS We performed electronic literature searches of the MEDLINE, PubMed, Embase and Cochrane Library databases for English-language articles from the earliest available date of indexing through 30 July 2019. We calculated the pooled sensitivity, specificity and diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) of 68Ga-SSTR PET and 18F-FDG PET in NET. We drew a summary receiver operator characteristic (SROC) curve and calculated the area under the curve (AUC) to measure the accuracy of 68Ga-SSTR PET and 18F-FDG PET in patients or lesions with NET. RESULTS Thirty studies comprising 3401 patients and 5793 lesions with NET were included in this meta-analysis. The pooled sensitivity, sensitivity, DOR and AUC for 68Ga-SSTR PET or PET/computed tomography (CT) in the diagnosis of NET, based on lesion patient, were 0.92(0.89-0.95), 0.91(0.83-0.95),119(51-282) and 0.96(0.94-0.98), and based on lesion, were 0.95(0.86-0.98), 0.93(0.83-0.97), 229(43-1205) and 0.98(0.96-0.99), respectively. The pooled sensitivity, sensitivity, DOR and AUC for 18F-FDG PET or PET/CT in NET were 0.70(0.41-0.89), 0.97(0.70-1.00), 67(7-612) and 0.94(0.92-0.96), respectively, when analyzed on a per-patient basis.The pooled sensitivities of 68Ga-SSTR PET/CT were 0.923 (95% CI: 0.884-0.952), 0.902 (0.862-0.934) and 0.578 (0.482-0.669) in the G1(ki67,≤2%), G2(ki67,>3%,≤20% and G3(ki67,>20%) groups based on patients with NET, respectively. The pooled sensitivities of 18F-FDG PET/CT were 0.378 (0.319-0.440), 0.554 (0.492-0.615) and 0.712 (0.633-0.783) in the G1, G2 and G3 groups based on patients with NET, respectively. CONCLUSION The 68Ga-SSTR PET has highly sensitive and had a greater diagnostic value than 18F-FDG PET for patients with NET. Fluorine-18-FDG PET, however, had significant specificity than 68Ga-SSTR PET. The 68Ga-SSTR has high sensitivity in G1/G2 NET, while 18F-FDG has a low positive rate. In G3 NET, however, the opposite is true. Therefore, the 68Ga-SSTR PET and 18F-FDG PET modalities are complementary rather than substitutive in clinical practice.