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Quantitative myocardial perfusion positron emission tomography and caffeine revisited with new insights on major adverse cardiovascular events and coronary flow capacity.
Kitkungvan, D, Bui, L, Johnson, NP, Patel, MB, Roby, AE, Vejpongsa, P, Babar, AK, Madjid, M, Nacimbene, A, Kumar, S, et al
European heart journal. Cardiovascular Imaging. 2019;(7):751-762
Abstract
AIMS: To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). METHODS AND RESULTS Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). CONCLUSION Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.
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Diagnostic value of radiolabeled amino acid PET for detection of pseudoprogression of brain tumor after treatment: a meta-analysis.
Kim, SJ, Ryul Shim, S
Nuclear medicine communications. 2019;(9):965-972
Abstract
PURPOSE The purpose of the current study was to investigate the diagnostic performance of radiolabeled amino acid PET for detection of pseudoprogression (PsP) of brain tumor after treatment through a systematic review and meta-analysis. METHODS The PubMed and EMBASE database, from the earliest available date of indexing through 15 February 2019, were searched for studies evaluating the diagnostic performance of radiolabeled amino acid PET for detection of PsP. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and constructed summary receiver operating characteristic (SROC) curves. RESULTS Across seven results from six studies (971 patients), the pooled sensitivity was 0.89 [95% confidence interval (CI): 0.82-0.94] without heterogeneity (I2 = 0.0) and a pooled specificity of 0.88 (95% CI: 0.76-0.94) without heterogeneity (I2=29.4). Likelihood ratio syntheses gave an overall positive likelihood ratio of 7.3 (95% CI: 3.6-14.7) and negative likelihood ratio of 0.12 (95% CI: 0.07-0.21). The pooled diagnostic odds ratio (DOR) was 60 (95% CI: 23-152). Hierarchical SROC curve indicates that the areas under the curve (AUC) was 0.92 (95% CI: 0.90-0.94). CONCLUSION The current meta-analysis showed the good sensitivity and specificity of radiolabeled amino acid PET for detection of PsP of brain tumor after treatment. Also, the DOR was high and SROC curve showed high AUC value.
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Molecular Coronary Plaque Imaging Using 18F-Fluoride.
Moss, AJ, Doris, MK, Andrews, JPM, Bing, R, Daghem, M, van Beek, EJR, Forsyth, L, Shah, ASV, Williams, MC, Sellers, S, et al
Circulation. Cardiovascular imaging. 2019;(8):e008574
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Abstract
BACKGROUND Coronary 18F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary 18F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased 18F-fluoride activity in coronary atherosclerotic plaque. METHODS In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial 18F-fluoride positron emission tomography. Coronary 18F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers. RESULTS Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 18F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, -0.01; 95% limits of agreement, -0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, -0.49 to 0.61). Good agreement in the categorization of focal 18F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values. CONCLUSIONS Coronary 18F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of 18F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110303 and NCT02278211.
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Copper-64 trastuzumab PET imaging: a reproducibility study.
Carrasquillo, JA, Morris, PG, Humm, JL, Smith-Jones, PM, Beylergil, V, Akhurst, T, O'donoghue, JA, Ruan, S, Modi, S, Hudis, CA, et al
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2019;(2):191-198
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BACKGROUND The current study aims to assess the safety, pharmacokinetics, feasibility, and reproducibility of immunoPET imaging with copper-64 (64Cu) trastuzumab. METHODS An IV injection of 296-370 MBq/5 mg 64Cu-trastuzumab was administered between 1 to 4 hours after routine trastuzumab treatment. Whole-body PET scans were performed immediately post-injection and at 24 hours post-injection. Serial pharmacokinetics were performed. Of 11 patients (median age of 52; range of 31-61), 8 underwent a repeat study with 64Cu-trastuzumab to assess image and pharmacokinetic reproducibility. Patients were monitored for toxicity. RESULTS Patients experienced no allergic reactions or significant adverse effects from 64Cu-trastuzumab. Eight patients successfully completed a repeat 64Cu-trastuzumab study, with acceptable reproducibility of both the biodistribution and pharmacokinetic clearance. Study 1 versus study 2 showed similar serum concentration post-injection (mean 42.4±7.8 %ID/L vs. 44.7±12.6 %ID/L) and similar T1/2 (single exponential 46.1 vs. 44.2 hours), P>0.5. The volume of distribution (median 2.50 L) was in the range reported for trastuzumab and close to the estimated plasma volume of 2.60 L. Of 11 patients, two had 64Cu-trastuzumab localization corresponding to known tumor sites - one in liver and one in breast. CONCLUSIONS Preliminary results suggest that scanning with 64Cu-trastuzumab is feasible, safe, and reproducible. Tumor uptake of 64Cu-trastuzumab was observed, but tumor detection exhibited low sensitivity in this study in which imaging was performed in the presence of trastuzumab therapy.
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Emerging topics and practical aspects for an appropriate use of amyloid PET in the current Italian context.
Nobili, F, Cagnin, A, Calcagni, ML, Chincarini, A, Guerra, UP, Morbelli, S, Padovani, A, Paghera, B, Pappatà, S, Parnetti, L, et al
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2019;(1):83-92
Abstract
In May 2017 some representatives of the Italian nuclear medicine and neurological communities spontaneously met to discuss the issues emerged during the first two years of routine application of amyloid PET with fluorinated radiopharmaceuticals in the real world. The limitations of a binary classification of scans, the possibility to obtain early images as a surrogate marker of regional cerebral bloos flow, the need for (semi-)quantification and, thus, the opportunity of ranking brain amyloidosis, the correlation with Aβ42 levels in the cerebrospinal fluid, the occurrence and biological meaning of uncertain/boderline scans, the issue of incidental amyloidosis, the technical pittfalls leading to false negative/positive results, the position of the tool in the diagnostic flow-chart in the national reality, are the main topics that have been discussed. Also, a card to justify the examination to be filled by the dementia specialist and a card for the nuclear medicine physician to report the exam in detail have been approved and are available in the web, which should facilitate the creation of a national register, as previewed by the 2015 intersocietal recommendation on the use of amyloid PET in Italy. The content of this discussion could stimulate both public institutions and companies to support further research on these topics.
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Selectivity of probes for PET imaging of dopamine D3 receptors.
Doot, RK, Dubroff, JG, Labban, KJ, Mach, RH
Neuroscience letters. 2019;:18-25
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Abstract
Dopamine D3 receptors have key roles in behavioral reward, addiction, Parkinson's disease, and schizophrenia, and there is interest in studying their role in these disorders using PET. However, current PET radiotracers for studying D3 receptors in humans all bind to both D2 and D3 due to similarities between the two receptors. Selective D2 and D3 radioligands would aid investigation of the differences between D2 and D3 circuitry in the central nervous system. While there are currently in vitro measures of ligand D3/D2 selectivity, there is a need for an in vivo PET measure of D3/D2 selectivity. This review discusses current PET imaging of dopamine D2/D3 receptors and proposes methodology for quantitating in vivo selectivity of probes for PET imaging of dopamine D3 receptors.
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Diagnostic and grading accuracy of 18F-FDOPA PET and PET/CT in patients with gliomas: a systematic review and meta-analysis.
Xiao, J, Jin, Y, Nie, J, Chen, F, Ma, X
BMC cancer. 2019;(1):767
Abstract
BACKGROUND Positron emission tomography (PET) and PET/computed tomography (PET/CT) imaging with 3,4-dihydroxy-6-[18F] fluoro-L-phenylalanine (18F-FDOPA) has been used in the evaluation of gliomas. We performed a meta-analysis to obtain the diagnostic and grading accuracy of 18F-FDOPA PET and PET/CT in patients with gliomas. METHODS PubMed, Embase, Cochrane Library and Web of Science were searched through 13 May 2019. We included studies reporting the diagnostic performance of 18F-FDOPA PET or PET/CT in glioma patients. Pooled sensitivity, specificity, and area under the summary receiver operating characteristic (SROC) curve were calculated from eligible studies on a per-lesion basis. RESULTS Eventually, 19 studies were included. Across 13 studies (370 patients) for glioma diagnosis, the pooled sensitivity and specificity of 18F-FDOPA PET and PET/CT were 0.90 (95%CI: 0.86-0.93) and 0.75 (95%CI: 0.65-0.83). Across 7 studies (219 patients) for glioma grading, 18F-FDOPA PET and PET/CT showed a pooled sensitivity of 0.88 (95%CI: 0.81-0.93) and a pooled specificity of 0.73 (95%CI: 0.64-0.81). CONCLUSIONS 18F-FDOPA PET and PET/CT demonstrated good performance for diagnosing gliomas and differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Further studies implementing standardized PET protocols and investigating the grading parameters are needed.
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Review of 18F-Fluciclovine PET for Detection of Recurrent Prostate Cancer.
Gusman, M, Aminsharifi, JA, Peacock, JG, Anderson, SB, Clemenshaw, MN, Banks, KP
Radiographics : a review publication of the Radiological Society of North America, Inc. 2019;(3):822-841
Abstract
Fluorine 18 (18F) fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC]) is a radiolabeled amino acid analog that takes advantage of the amino acid transport upregulation in several types of cancer cells. FACBC is taken up to a greater extent in prostate cancer cells than in surrounding normal tissue, providing an opportunity for its use in cases of this common cancer. In 2016, the U.S. Food and Drug Administration found the accuracy of FACBC PET to be superior to that of other molecular imaging techniques and subsequently granted approval for its use in PET of recurrent prostate cancer. As FACBC is an 18F radiotracer, an on-site cyclotron is not required for its production. This feature enables the widespread clinical availability of this agent and, in turn, an opportunity for improved patient care. The clinical pharmacology and imaging features of FACBC are reviewed, and the role of this agent in the imaging of recurrent prostate cancer, within the context of research that supports its effectiveness, is discussed. The administration of and image acquisition facilitated by using FACBC, as compared with 18F fluorodeoxyglucose, which is more widely used, are described. In addition, the criteria for interpreting FACBC imaging findings are outlined, with emphasis on common causes of false-positive and false-negative findings. ©RSNA, 2019.
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Utility of Molecular Imaging with 2-Deoxy-2-[Fluorine-18] Fluoro-DGlucose Positron Emission Tomography (18F-FDG PET) for Small Cell Lung Cancer (SCLC): A Radiation Oncology Perspective.
Sager, O, Dincoglan, F, Demiral, S, Uysal, B, Gamsiz, H, Elcim, Y, Gundem, E, Dirican, B, Beyzadeoglu, M
Current radiopharmaceuticals. 2019;(1):4-10
Abstract
BACKGROUND AND OBJECTIVE Although accounting for a relatively small proportion of all lung cancers, small cell lung cancer (SCLC) remains to be a global health concern with grim prognosis. Radiotherapy (RT) plays a central role in SCLC management either as a curative or palliative therapeutic strategy. There has been considerable progress in RT of SCLC, thanks to improved imaging techniques leading to accurate target localization for precise delivery of RT. Positron emission tomography (PET) is increasingly used in oncology practice as a non-invasive molecular imaging modality. METHODS Herein, we review the utility of molecular imaging with 2-deoxy-2-[fluorine-18] fluoro-Dglucose PET (18F-FDG PET) for SCLC from a radiation oncology perspective. RESULTS There has been extensive research on the utility of PET for SCLC in terms of improved staging, restaging, treatment designation, patient selection for curative/palliative intent, target localization, response assessment, detection of residual/recurrent disease, and prediction of treatment outcomes. CONCLUSION PET provides useful functional information as a non-invasive molecular imaging modality and may be exploited to improve the management of patients with SCLC. Incorporation of PET/CT in staging of patients with SCLC may aid in optimal treatment allocation for an improved therapeutic ratio. From a radiation oncology perspective, combination of functional and anatomical data provided by integrated PET/CT improves discrimination between atelectasis and tumor, and assists in the designation of RT portals with its high accuracy to detect intrathoracic tumor and nodal disease. Utility of molecular imaging for SCLC should be further investigated in prospective randomized trials to acquire a higher level of evidence for future potential applications of PET.
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Fluorodeoxyglucose PET for Monitoring Response to Embolotherapy (Transarterial Chemoembolization) in Primary and Metastatic Liver Tumors.
Schobert, I, Chapiro, J, Pucar, D, Saperstein, L, Savic, LJ
PET clinics. 2019;(4):437-445
Abstract
Response to transarterial chemoembolization (TACE) in patients with liver cancer is commonly assessed on MRI or CT to quantify tumor necrosis and morphologic changes that occur gradually. However, the efficacy of embolotherapies remains limited because of local recurrence, as treated tumors demonstrate individual molecular characteristics that alter susceptibility and response to embolotherapies. Upregulation of cancer cell glycolysis can be detected by fluorine-18-fluorodeoxyglucose PET. Therefore, the combination of functional (PET) with commonly used cross-sectional imaging techniques (MRI, CT) can help characterize and monitor liver tumors with the potential to improve TACE toward becoming a more personalized and tumor microenvironment-directed therapy.