été A Model of Community-Based Behavioral Intervention for Depression in Diabetes: Program ACTIVE By spectrum.diabetesjournals.org Published On :: 2010-01-01 Mary de GrootJan 1, 2010; 23:18-25From Research to Practice Full Article
été Complementary and Integrative Medicine: Emerging Therapies for Diabetes, Part 1: Preface By spectrum.diabetesjournals.org Published On :: 2001-08-01 Cynthia PayneAug 1, 2001; 14:Preface Full Article
été Nutritional Management of Gastroparesis in People With Diabetes By spectrum.diabetesjournals.org Published On :: 2007-10-01 Carol Rees ParrishOct 1, 2007; 20:231-234Nutrition FYI Full Article
été Integrating Depression Care With Diabetes Care in Real-World Settings: Lessons From the Robert Wood Johnson Foundation Diabetes Initiative By spectrum.diabetesjournals.org Published On :: 2007-01-01 Daren AndersonJan 1, 2007; 20:10-16Feature Articles Full Article
été Select Vitamins and Minerals in the Management of Diabetes By spectrum.diabetesjournals.org Published On :: 2001-08-01 Belinda S. OConnellAug 1, 2001; 14:Articles Full Article
été A Novel Approach to Adolescents With Type 1 Diabetes: The Team Clinic Model By spectrum.diabetesjournals.org Published On :: 2015-02-01 Jennifer K. RaymondFeb 1, 2015; 28:68-71Care Innovations Full Article
été A High Level of Patient Activation Is Observed But Unrelated to Glycemic Control Among Adults With Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2010-07-01 Robert MayberryJul 1, 2010; 23:171-176Feature Articles Full Article
été Transitions in Care from the Hospital to Home for Patients With Diabetes By spectrum.diabetesjournals.org Published On :: 2014-08-01 Karen B. HirschmanAug 1, 2014; 27:192-195From Research to Practice Full Article
été Depressive Affect Among Four Ethnic Groups of Male Patients With Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2004-10-01 Lawrence FisherOct 1, 2004; 17:215-219Articles Full Article
été Polypharmacy as a Risk Factor in the Treatment of Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2006-01-01 Roger P. AustinJan 1, 2006; 19:13-16Pharmacy Update Full Article
été Educator Experience with the U.S. Diabetes Conversation Map(R) Education Program in the Journey for Control of Diabetes: The IDEA Study By spectrum.diabetesjournals.org Published On :: 2010-07-01 Omar D. FernandesJul 1, 2010; 23:194-198Care Innovations Full Article
été From DSME to DSMS: Developing Empowerment-Based Diabetes Self-Management Support By spectrum.diabetesjournals.org Published On :: 2007-10-01 Martha Mitchell FunnellOct 1, 2007; 20:221-226Articles Full Article
été Redesign of a Diabetes System of Care Using an All-or-None Diabetes Bundle to Build Teamwork and Improve Intermediate Outcomes By spectrum.diabetesjournals.org Published On :: 2010-07-01 Frederick J. BloomJul 1, 2010; 23:165-169From Research to Practice Full Article
été Improving Diabetes Care in the Hospital Using Guideline-Directed Orders By spectrum.diabetesjournals.org Published On :: 2001-10-01 Stephen F. QuevedoOct 1, 2001; 14:Feature Articles Full Article
été Negotiating the Barrier of Hypoglycemia in Diabetes By spectrum.diabetesjournals.org Published On :: 2002-01-01 Philip E. CryerJan 1, 2002; 15:Articles Full Article
été Management of Type 1 Diabetes in Older Adults By spectrum.diabetesjournals.org Published On :: 2014-02-01 Ruban DhaliwalFeb 1, 2014; 27:9-20Research to Practice Full Article
été Psychosocial Barriers to Diabetes Self-Management and Quality of Life By spectrum.diabetesjournals.org Published On :: 2001-01-01 Russell E. GlasgowJan 1, 2001; 14:Articles Full Article
été Diabetes Self-Management Education for Older Adults: General Principles and Practical Application By spectrum.diabetesjournals.org Published On :: 2006-10-01 Emmy SuhlOct 1, 2006; 19:234-240Articles Full Article
été Motivational Interviewing and Diabetes: What Is It, How Is It Used, and Does It Work? By spectrum.diabetesjournals.org Published On :: 2006-01-01 Garry WelchJan 1, 2006; 19:5-11Lifestyle and Behavior Full Article
été Making a Difference With Interactive Technology: Considerations in Using and Evaluating Computerized Aids for Diabetes Self-Management Education By spectrum.diabetesjournals.org Published On :: 2001-04-01 Russell E. GlasgowApr 1, 2001; 14:Feature Articles Full Article
été Self-Management Goal Setting in a Community Health Center: The Impact of Goal Attainment on Diabetes Outcomes By spectrum.diabetesjournals.org Published On :: 2010-04-01 Daren R. AndersonApr 1, 2010; 23:97-105Feature Articles Full Article
été Association of Self-Efficacy and Self-Care With Glycemic Control in Diabetes By spectrum.diabetesjournals.org Published On :: 2013-08-01 Carla Moore BeckerleAug 1, 2013; 26:172-178Feature Articles Full Article
été Stress and Diabetes: A Review of the Links By spectrum.diabetesjournals.org Published On :: 2005-04-01 Cathy LloydApr 1, 2005; 18:121-127Feature Articles Full Article
été A Review of Volunteer-Based Peer Support Interventions in Diabetes By spectrum.diabetesjournals.org Published On :: 2011-05-01 Tricia S. TangMay 1, 2011; 24:85-98From Research to Practice/Behavioral Interventions for Diabetes Self-Management Full Article
été Associations Between Self-Management Education and Comprehensive Diabetes Clinical Care By spectrum.diabetesjournals.org Published On :: 2010-01-01 Tammie M. JohnsonJan 1, 2010; 23:41-46Feature Articles Full Article
été Overview of Peer Support Models to Improve Diabetes Self-Management and Clinical Outcomes By spectrum.diabetesjournals.org Published On :: 2007-10-01 Michele HeislerOct 1, 2007; 20:214-221Articles Full Article
été Diabetes Legal Advocacy Comes of Age By spectrum.diabetesjournals.org Published On :: 2006-07-01 Michael A. GreeneJul 1, 2006; 19:171-179Feature Articles Full Article
été Family Conflict and Diabetes Management in Youth: Clinical Lessons From Child Development and Diabetes Research By spectrum.diabetesjournals.org Published On :: 2004-01-01 Barbara J. AndersonJan 1, 2004; 17:Articles Full Article
été Implementing Diabetes Self-Management Education in Primary Care By spectrum.diabetesjournals.org Published On :: 2006-04-01 Sharlene EmersonApr 1, 2006; 19:79-83Articles Full Article
été Group Education in Diabetes: Effectiveness and Implementation By spectrum.diabetesjournals.org Published On :: 2003-04-01 Carolé R. MensingApr 1, 2003; 16:Articles Full Article
été Four Theories and a Philosophy: Self-Management Education for Individuals Newly Diagnosed With Type 2 Diabetes By spectrum.diabetesjournals.org Published On :: 2003-04-01 T. Chas SkinnerApr 1, 2003; 16:Lifestyle and Behavior Full Article
été The Diabetes Attitudes, Wishes, and Needs (DAWN) Program: A New Approach to Improving Outcomes of Diabetes Care By spectrum.diabetesjournals.org Published On :: 2005-07-01 Soren E. SkovlundJul 1, 2005; 18:136-142Lifestyle and Behavior Full Article
été Determination of globotriaosylceramide analogs in the organs of a mouse model of Fabry disease [Lipids] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease. Full Article
été Investigation of inter- and intra-tumoral heterogeneity of glioblastoma using TOF-SIMS By feedproxy.google.com Published On :: 2020-04-06 Samvel K GularyanApr 6, 2020; 0:RA120.001986v1-mcp.RA120.001986Research Full Article
été Characterization of signaling pathways associated with pancreatic {beta}-cell adaptive flexibility in compensation of obesity-linked diabetes in db/db mice By feedproxy.google.com Published On :: 2020-04-07 Taewook KangApr 7, 2020; 0:RA119.001882v1-mcp.RA119.001882Research Full Article
été A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients By feedproxy.google.com Published On :: 2020-04-01 Dorte B. Bekker-JensenApr 1, 2020; 19:716-729Technological Innovation and Resources Full Article
été Peter Watkins By feedproxy.google.com Published On :: Mon, 17 Jun 2019 14:01:46 +0000 Associate Fellow, International Security Programme Biography Peter Watkins became an associate fellow for Chatham House in June 2019. Before that, from 2014 to 2018, he was Director General (DG) in the UK Ministry of Defence (MoD) responsible for strategic defence policy, including key multilateral and bilateral relationships (such as NATO), nuclear, cyber, space and prosperity (latterly this post was known as the DG Strategy and International).Previously he served as DG of the Defence Academy, Director of Operational Policy, Director responsible for the UK share of the multinational Typhoon combat aircraft programme and as Defence Counsellor in the UK Embassy in Berlin.He is a frequent participant in conferences on defence and security in the UK and overseas.He was awarded the CB (2019) and CBE (2004) for services to defence. He has an MA from Cambridge University. Areas of expertise European securityDeterrence policyNuclear policyStabilisation and peacekeepingInternational armaments cooperation Past experience 2006-07Fellow, Weatherhead Center for International Affairs, Harvard University1993-94Senior course member, NATO Defense College 07775 925762 Email LinkedIn Full Article
été Deterrence Perspectives in the 21st Century By feedproxy.google.com Published On :: Fri, 28 Feb 2020 09:36:23 +0000 The aim of this project is to provide a space to explore creative/disruptive ideas in order to make headway on perspectives concerning deterrence. This will encourage ‘responsible disruption’ in the nuclear field. Concerns about transatlantic security are high following the US 2018 Nuclear Posture Review and its interpretation of the Russian doctrine, the demise of the Intermediate Range Nuclear Forces Treaty (INF), the uncertainty surrounding the potential extension of the New Strategic Arms Reduction Treaty (New START), and Russian deployment of Avangard hypersonic, nuclear-capable missile systems.Emerging technologies, especially quantum technologies, jeopardize the reliability of existing encryption measures. Some of the most sophisticated cyber attacks are already assisted by artificial intelligence. The possibility that nuclear weapons systems can be interfered with both during conflict and peacetime by these technologies, without the knowledge of the possessor state, raises questions on the reliability and integrity of these systems, with implications for military decision-making, particularly to deterrence policy.These issues and more indicate the changes in the security landscape that have a bearing on the future of nuclear deterrence.This project is supported by the Hiroshima Prefecture and Government of Ireland. Latest (1) Research paper Perspectives on Nuclear Deterrence in the 21st Century 20 April 2020 Research & Publications (1) Research paper Perspectives on Nuclear Deterrence in the 21st Century 20 April 2020 Full Article
été Perspectives on Nuclear Deterrence in the 21st Century By feedproxy.google.com Published On :: Sun, 19 Apr 2020 19:32:28 +0000 20 April 2020 Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in the 21st century. Researchers at Chatham House have worked with eight experts to produce this collection of essays examining four contested themes in contemporary policymaking on deterrence. Read online Download PDF Dr Beyza Unal Senior Research Fellow, International Security Programme @beyzaunal Google Scholar Yasmin Afina Research Assistant, International Security Programme @afinayasmin LinkedIn Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary Dr John Borrie Associate Fellow, International Security Programme Google Scholar Dr Jamie Shea Associate Fellow, International Security Programme LinkedIn Peter Watkins Associate Fellow, International Security Programme LinkedIn Dr Maria Rost Rublee Associate Professor of International Relations, Monash University Cristina Varriale Research Fellow in Proliferation and Nuclear Policy, RUSI Dr Tanya Ogilvie-White Adjunct Senior Fellow, Griffith Asia Institute, Griffith University Dr Andrew Futter Associate Professor of International Politics, University of Leicester Christine Parthemore Chief Executive Officer, Council on Strategic Risks (CSR) 2020-04-20-NuclearDeterrence.jpeg Royal Navy Vanguard Class submarine HMS Vigilant returning to HMNB Clyde after extended deployment. The four Vanguard-class submarines form the UK's strategic nuclear deterrent force. Photo: Ministry of Defence. SummaryThis collection of essays explores, from the perspectives of eight experts, four areas of deterrence theory and policymaking: the underlying assumptions that shape deterrence practice; the enduring value of extended deterrence; the impact of emerging technologies; and the ‘blurring’ of the lines between conventional and nuclear weapons.Nuclear deterrence theory, with its roots in the Cold War era, may not account for all eventualities in security and defence in the 21st century, given the larger number of nuclear actors in a less binary geopolitical context. It is clear that a number of present factors challenge the overall credibility of ‘classical’ nuclear deterrence, meaning that in-depth analysis is now needed.Uncertainty as to the appetite to maintain the current nuclear weapons policy architecture looms large in discussions and concerns on global and regional security. The demise of the Intermediate-Range Nuclear Forces Treaty, doubts over the potential extension of the New Strategic Arms Reduction Treaty, heightened regional tensions in Northeast and South Asia, together with the current and likely future risks and challenges arising from global technological competition, making it all the more urgent to examine long-held assumptions in the real-world context.Extended deterrence practices differ from region to region, depending on the domestic and regional landscape. Increased focus on diplomatic capabilities to reduce risks and improve the long-term outlook at regional level, including by spearheading new regional arms-control initiatives, may be a viable way forward. Addressing the bigger picture – notably including, on the Korean peninsula, Pyongyang’s own threat perception – and the links between conventional and nuclear missile issues will need to remain prominent if long-term and concrete changes are to take hold.Most states have long held nuclear weapons to be ‘exceptional’: their use would represent a dramatic escalation of a conflict that must never be attained. Latterly, however, some officials and scholars have made the case that the impact of the use of a low-yield nuclear weapon would not be entirely distinct from that of a large-scale conventional attack. This blurring of lines between conventional and nuclear deterrence strips nuclear weapons of their exceptional nature, in a context in which states are faced with diverse, complex and concurrent threats from multiple potential adversaries that are able to synchronize non-military and military options, up to and including nuclear forces. The use of nuclear weapons risks becoming a ‘new normal’, potentially reducing the threshold for use – to cyberattacks, for example. This has direct implications for discussions around strategic stability. While emerging technologies may offer tremendous opportunities in the modernization of nuclear weapons, they also present major risks and destabilizing challenges. Artificial intelligence, automation, and other developments in the cyber sphere affect dynamics on both the demand and supply sides of the nuclear deterrence equation. States and alliance such as NATO must adapt their deterrence thinking in light of these technological developments, and define their primary purpose and priorities in this shifting security context. Resilience planning, adaptation to the evolving security environment, threat anticipation, and consistent crisis management and incident response – as well as thinking about the mitigation measures necessary to prevent conflict escalation should deterrence fail – will all be critical in upholding nuclear deterrence as both policy and practice. Department/project International Security Programme, Deterrence Perspectives in the 21st Century Full Article
été Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis By diabetes.diabetesjournals.org Published On :: 2020-02-20T11:55:30-08:00 Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb– relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction. Full Article
été PARP-1-targeted Auger emitters display high-LET cytotoxic properties in vitro but show limited therapeutic utility in solid tumor models of human neuroblastoma By jnm.snmjournals.org Published On :: 2019-11-01T13:36:37-07:00 The currently available therapeutic radiopharmaceutical for high-risk neuroblastoma, 131I-MIBG, is ineffective at targeting micrometastases due to the low linear energy transfer (LET) properties of high-energy beta particles. In contrast, Auger radiation has high-LET properties with nanometer ranges in tissue, efficiently causing DNA damage when emitted in close proximity to DNA. The aim of this study was to evaluate the cytotoxicity of targeted Auger therapy in pre-clinical models of high-risk neuroblastoma. Methods: Using a radiolabeled poly(ADP-ribose) polymerase (PARP) inhibitor, 125I-KX1, we delivered an Auger emitter iodine-125 to PARP-1: a chromatin-binding enzyme overexpressed in neuroblastoma. In vitro cytotoxicity of 125I-KX1 was assessed in nineteen neuroblastoma cell lines, followed by in-depth pharmacological analysis in a sensitive and resistant pair of cell lines. Immunofluorescence microscopy was used to characterize 125I-KX1-induced DNA damage. Finally, in vitro/in vivo microdosimetry was modeled from experimentally derived pharmacological variables. Results: 125I-KX1 was highly cytotoxic in vitro across a panel of neuroblastoma cell lines, directly causing double strand DNA breaks. Based on subcellular dosimetry, 125I-KX1 was approximately twice as effective compared to 131I-KX1, whereas cytoplasmic 125I-MIBG demonstrated low biological effectiveness. Despite the ability to deliver focused radiation dose to the cell nuclei, 125I-KX1 remained less effective than its alpha-emitting analog 211At-MM4, and required significantly higher activity for equivalent in vivo efficacy based on tumor microdosimetry. Conclusion: Chromatin-targeted Auger therapy is lethal to high-risk neuroblastoma cells with potential use in micrometastatic disease. This study provides the first evidence for cellular lethality from a PARP-1 targeted Auger emitter, calling for further investigation into targeted Auger therapy. Full Article
été Evaluation of dosimetry, quantitative methods and test-retest variability of 18F-PI-2620 PET for the assessment of tau deposits in the human brain By jnm.snmjournals.org Published On :: 2019-11-11T12:55:20-08:00 18F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of 18F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: 18F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for 18F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static 18F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV. Full Article
été Initial studies with [11C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR>1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR <1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR>1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR<1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions. Full Article
été Diagnostic value of 68Ga-PSMA PET/CT for detection of PTEN expression in prostate cancer: a pilot study By jnm.snmjournals.org Published On :: 2019-11-22T10:43:33-08:00 Purpose: To explore the value of 68Ga-PSMA-PET/CT for detection of phosphatase and tensin homolog (PTEN) - loss prostate cancer (PCa). Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathological images and regions of interest were drawn on matched mpMRI and PET/CT images. Imaging parameters including average apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were derived. Immunohistochemical staining was carried out to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver operating characteristics (ROC) analysis. A univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: Totally, 103 lesions from 54 patients were analyzed. Of these lesions, 34 of 103 (33.0%) showed PTEN-loss status. Our study showed a strong association between SUVmax and PTEN-loss tumors both in the per-patient analysis (P < 0.01) and per-lesion analysis (P < 0.01), yielding the sensitivity and specificity of 0.80 and 0.77 in the per-patient analysis and 0.83 and 0.74 in the per-lesion analysis. Meanwhile, higher pathological PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters including ADCmean (P > 0.05) and PI-RADS score (P > 0.05). Surprisingly, SUVmax was a significant predictor for detection of PTEN-loss tumors (odds ratio: 7.56, 95% confidence interval: 2.18-26.24, per-patient analysis; odds ratio: 13.66, 95% confidence interval: 4.32-43.24, per-lesion analysis). Conclusion: 68Ga-PSMA-PET/CT could effectively detect aggressive PTEN-loss tumors. Full Article
été Inflammation-based index and 68Ga-DOTATOC PET-derived uptake and volumetric parameters predict outcome in neuroendocrine tumor patients treated with 90Y-DOTATOC By jnm.snmjournals.org Published On :: 2019-12-05T10:37:41-08:00 We performed post-hoc analyses on the utility of pre-therapeutic and early interim 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography (PET) tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to four cycles of 1.85 GBq/m²/cycle 90Y-DOTATOC with a maximal kidney biologic effective dose of 37 Gy. All patients underwent a 68Ga-DOTATOC PET/computed tomography (CT) at baseline and seven weeks after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semi-automatically delineated using a customized standardized uptake value (SUV) threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival (PFS) and overall survival (OS) were 13.9 and 22.3 months, respectively. An SUVmean higher than 13.7 (75th percentile (P75)) was associated with better survival (hazard ratio (HR) 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 ml (P75) was associated with worse OS (HR 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with PFS were found. A composite score based on SUVmean and IBI allowed to further stratify patients in three categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (P75) was associated with worse survival (HR 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization. Full Article
été Quantitative test-retest measurement of 68Ga-PSMA-HBED-CC (PSMA-11) in tumor and normal tissue By jnm.snmjournals.org Published On :: 2019-12-05T10:37:42-08:00 The PET radiotracer 68Ga-PSMA-HBED-CC (68Ga-PSMA-11) shows potential as an imaging biomarker for recurrent and metastatic prostate cancer. The purpose of this study was to determine repeatability of 68Ga-PSMA-HBED-CC in a test-retest trial in subjects with metastatic prostate adenocarcinoma. Methods: Subjects with metastatic prostate cancer underwent two PET/CT scans with 68Ga-PSMA-HBED-CC within 14 days (mean 6 ± 4 d). Lesions in bone, nodes, prostate/bed, and visceral organs as well as representative normal tissues (salivary glands and spleen) were segmented separately by two readers. Absolute and percent differences in SUVmax and SUVmean were calculated for all test-retest regions. Repeatability was assessed using percentage difference, within-subject coefficient of variation (wCV), repeatability coefficient (RC), and Bland-Altman analysis. Results: 18 subjects were evaluated, 16 of which demonstrated local or metastatic disease on 68Ga-PSMA-HBED-CC PET/CT. A total of 136 lesions were segmented in bone (n = 99), nodes (n = 27), prostate/bed (n = 7), and viscera (n = 3). The wCV for SUVmax was 11.7% for bone lesions and 13.7% for nodes. The RC was ±32.5% SUVmax for bone lesions and ±37.9% SUVmax for nodal lesions, meaning 95% of the normal variability between two measurements will be within these numbers, so larger differences are likely attributable to true biological changes in tumor rather than normal physiologic or measurement variability. wCV in the salivary glands and spleen was 8.9% and 10.7% SUVmean, respectively. Conclusion: Repeatability measurements for PET/CT test-retest with 68Ga-PSMA-HBED-CC show a wCV 12-14% SUVmax and RC ±33-38% SUVmax in bone and nodal lesions. These estimates are an important aspect of 68Ga-PSMA-HBED-CC as a quantitative imaging biomarker. These estimates are similar to those reported for 18F-FDG, suggesting that 68Ga-PSMA-HBED-CC PET/CT may be useful in monitoring response to therapy. Full Article
été Early Detection in a Mouse Model of Pancreatic Cancer by Imaging DNA Damage Response Signalling By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Rationale: Despite its widespread use in oncology, the PET radiotracer 18F-FDG is ineffective for improving early detection of pancreatic ductal adenocarcinoma (PDAC). An alternative strategy for early detection of pancreatic cancer involves visualisation of high-grade pancreatic intraepithelial neoplasias (PanIN-3), generally regarded as the non-invasive precursors of PDAC. The DNA damage response is known to be hyper-activated in late-stage PanINs. Therefore, we investigated whether the SPECT imaging agent, 111In-anti-H2AX-TAT, allows visualisation of the DNA damage repair marker H2AX in PanIN-3s in an engineered mouse model of PDAC, to facilitate early detection of PDAC. Methods: Genetically engineered KPC mice (KRasLSL.G12D/+; p53LSL.R172H/+; PdxCre) were imaged with 18F-FDG and 111In-anti-H2AX-TAT. PanIN/PDAC presence visualised by histology was compared with autoradiography and immunofluorescence. Separately, the survival of KPC mice imaged with 111In-anti-H2AX-TAT was evaluated. Results: In KPC mouse pancreata, H2AX expression was increased in high-grade PanINs, but not in PDAC, corroborating earlier results obtained from human pancreas sections. Uptake of 111In-anti-H2AX-TAT, but not 111In-IgG-TAT or 18F-FDG, within the pancreas was positively correlated with the age of KPC mice, which was correlated with the number of high-grade PanINs. 111In-anti-H2AX-TAT localises preferentially in high-grade PanIN lesions, but not in established PDAC. Younger, non-tumour-bearing KPC mice that show uptake of 111In-anti-H2AX-TAT in the pancreas survive significantly shorter than mice with physiological 111In-anti-H2AX-TAT uptake. Conclusion: 111In-anti-H2AX-TAT imaging allows non-invasive detection of DNA damage repair signalling upregulation in pre-invasive PanIN lesions and is a promising new tool to aid in the early detection and staging of pancreatic cancer. Full Article
été 177Lu-NM600 targeted radionuclide therapy extends survival in syngeneic murine models of triple-negative breast cancer By jnm.snmjournals.org Published On :: 2019-12-20T13:25:42-08:00 Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer leading to the worst prognosis. Because current therapeutic approaches lack efficacy, there is a clinically unmet need for effective treatment alternatives. Herein, we demonstrate a promising strategy utilizing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with 177Lu for targeted radionuclide therapy (TRT) of TNBC. In two murine syngeneic models of TNBC, we confirmed excellent tumor targeting and rapid normal tissue clearance of the PET imaging analog 86Y-NM600. Based on longitudinal PET/CT data acquired with 86Y-NM600, we estimated the dosimetry of therapeutic 177Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of 177Lu-NM600 resulted in significant tumor growth inhibition and prolonged overall survival in mice bearing syngeneic 4T07 and 4T1 tumors. Complete response was attained in 60% of 4T07 bearing mice, but animals carrying aggressive 4T1 tumor grafts succumbed to metastatic progression. The injected activities used for treatment (9.25 and 18.5 MBq) were well tolerated, and only mild transient cytopenia was noted. Overall, our results suggest that 177Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting. Full Article
été Targeted optical imaging of the glucagon-like peptide 1 receptor using exendin-4-IRDye800CW By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Rationale: The treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (CHI) is surgery. However, intra-operative detection can be challenging. This could be overcome with intra-operative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. Here, a novel method for targeted near-infrared (NIR) fluorescence imaging of glucagon-like peptide 1 receptor (GLP-1R) positive lesions, using the GLP-1 agonist exendin-4, labeled with IRDye800CW, was examined in vitro and in vivo. Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. In vivo NIR fluorescence imaging of CHL-GLP-1R xenografts was performed. Localization of the tracer in the pancreatic islets of BALB/c nude mice was examined using fluorescence microscopy. Laparoscopic imaging was performed to detect the fluorescent signal of the tracer in the pancreas of mini pigs. Results: Exendin-4-IRDye800CW binds the GLP-1R with an IC50 value of 3.96 nM. The tracer accumulates in CHL-GLP-1R xenografts. Subcutaneous CHL-GLP-1R xenografts were visualized using in vivo NIR fluorescence imaging. The tracer accumulates specifically in the pancreatic islets of mice and a clear fluorescent signal was detected in the pancreas of mini pigs. Conclusion: These date provide the first in vivo evidence of the feasibility of targeted fluorescence imaging of GLP-1R positive lesions. Intra-operative lesion delineation using exendin-4-IRDye800CW could benefit open as well as laparoscopic surgical procedures for removal of insulinomas and focal lesions in CHI. Full Article
été 11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of Beta-Cell-Mass in Patients with Type-1 Diabetes By jnm.snmjournals.org Published On :: 2020-01-10T04:59:09-08:00 Full Article