27 results on '"Ripa, Rasmus Sejersten"'
Search Results
2. Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials
- Author
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Wretlind, Asger, Curovic, Viktor Rotbain, de Zawadzki, Andressa, Suvitaival, Tommi, Xu, Jin, Zobel, Emilie Hein, von Scholten, Bernt Johan, Ripa, Rasmus Sejersten, Kjaer, Andreas, Hansen, Tine Willum, Vilsbøll, Tina, Vestergaard, Henrik, Rossing, Peter, and Legido-Quigley, Cristina
- Published
- 2023
- Full Text
- View/download PDF
3. Feasibility of positron range correction in 82-Rubidium cardiac PET/CT
- Author
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Jensen, Malte, Bentsen, Simon, Clemmensen, Andreas, Jensen, Jacob Kildevang, Madsen, Johanne, Rossing, Jonas, Laier, Anna, Hasbak, Philip, Kjaer, Andreas, and Ripa, Rasmus Sejersten
- Published
- 2022
- Full Text
- View/download PDF
4. 3D whole body preclinical micro-CT database of subcutaneous tumors in mice with annotations from 3 annotators.
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Jensen, Malte, Clemmensen, Andreas, Hansen, Jacob Gorm, van Krimpen Mortensen, Julie, Christensen, Emil N., Kjaer, Andreas, and Ripa, Rasmus Sejersten
- Subjects
X-ray computed microtomography ,DATABASES ,ANTINEOPLASTIC agents ,TOMOGRAPHY ,ANIMAL models in research - Abstract
A pivotal animal model for development of anticancer molecules is mice with subcutaneous tumors, grown by injection of xenografted tumor cells, where micro-Computed Tomography (µCT) of the mice is used to analyze the efficacy of the anticancer molecule. Manual delineation of the tumor region is necessary for the analysis, which is time-consuming and inconsistent, highlighting the need for automatic segmentation (AS) tools. This study introduces a preclinical µCT database, comprising 452 whole-body scans from 223 individual mice with subcutaneous tumors, spanning ten diverse µCT datasets conducted between 2014 and 2020 on a preclinical PET/CT scanner, making it the hitherto largest dataset of its kind. Each tumor is annotated manually by three expert annotators, allowing for robust model development. Inter-annotator agreement was analyzed, and we report an overall annotation agreement of 0.903 ± 0.046 (mean ± std) Fleiss' Kappa and a mean deviation in volume estimation of 0.015 ± 0.010 cm
3 (6.9% ± 4.7), which establishes a human baseline accuracy for delineation of subcutaneous tumors, while showing good inter-annotator agreement. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
5. Detection of infective endocarditis with [64Cu]Cu-DOTATATE positron emission tomography/computed tomography: a case series.
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Hadji-Turdeghal, Katra, Fosbøl, Marie Øbro, Hasbak, Philip, Kjaer, Andreas, Køber, Lars, Ripa, Rasmus Sejersten, and Fosbøl, Emil Loldrup
- Subjects
POSITRON emission tomography ,INFECTIVE endocarditis ,COMPUTED tomography ,MITRAL stenosis ,AORTIC stenosis ,GASTROINTESTINAL stromal tumors - Abstract
Background Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[
18 F]fluoro- D- glucose positron emission tomography/computed tomography ([18 F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64 Cu]Cu-DOTATATE ([64 Cu]Cu-[1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate). Case summary An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64 Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64 Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis. Discussion In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64 Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
6. Early Detection of Cardiotoxicity Using [64Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure.
- Author
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Hoeeg, Cecilie, Follin, Bjarke, Grandjean, Constance Eline, Ripa, Rasmus Sejersten, Ekblond, Annette, Kastrup, Jens, Binderup, Tina, and Kjaer, Andreas
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- 2024
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- View/download PDF
7. Effect of Alirocumab on Carotid Inflammation by [18F]FDG PET in Patients with Acute Myocardial Infarction
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Bang, Lia E., primary, Jensen, Jacob Kildevang, additional, Räber, Lorenz, additional, Koskinas, Konstantinos C., additional, Bär, Sarah, additional, Losdat, Sylvain, additional, Matter, Christian M., additional, Lonborg, Jacob, additional, Radu Juul Jensen, Maria D., additional, Kjaer, Andreas, additional, Engstrøm, Thomas, additional, and Ripa, Rasmus Sejersten, additional
- Published
- 2024
- Full Text
- View/download PDF
8. Increased sub-clinical coronary artery pathology in type 2 diabetes with albuminuria
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Rasmussen, Ida Kirstine Bull, Skriver-Moeller, Anne-Cathrine, Ripa, Rasmus Sejersten, Hasbak, Philip, Wasehuus, Victor Soendergaard, Hadji-Turdeghal, Katra, Zobel, Emilie Hein, Lassen, Martin Lyngby, Holmvang, Lene, Slomka, Piotr, Rossing, Peter, Kjaer, Andreas, Hansen, Tine Willum, Rasmussen, Ida Kirstine Bull, Skriver-Moeller, Anne-Cathrine, Ripa, Rasmus Sejersten, Hasbak, Philip, Wasehuus, Victor Soendergaard, Hadji-Turdeghal, Katra, Zobel, Emilie Hein, Lassen, Martin Lyngby, Holmvang, Lene, Slomka, Piotr, Rossing, Peter, Kjaer, Andreas, and Hansen, Tine Willum
- Abstract
Diabetes affects the kidneys, and presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advantages in non-invasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of sub-clinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (18F-sodium fluoride positron emission tomography/computed tomography (PET/CT), plaque inflammation (64Cu- DOTATATE PET/CT) and myocardial flow reserve (82Rubidium PET/CT). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin creatinine ratio (UACR) ≥ 30 mg/g)), and 30 had normoalbuminuria (UACR < 30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particularly higher levels of microcalcifications and impaired myocardial microvascular function, however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome.
- Published
- 2024
9. Increased sub-clinical coronary artery pathology in type 2 diabetes with albuminuria
- Author
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Rasmussen, Ida Kirstine Bull, primary, Skriver-Moeller, Anne-Cathrine, additional, Ripa, Rasmus Sejersten, additional, Hasbak, Philip, additional, Wasehuus, Victor Soendergaard, additional, Hadji-Turdeghal, Katra, additional, Zobel, Emilie Hein, additional, Lassen, Martin Lyngby, additional, Holmvang, Lene, additional, Slomka, Piotr, additional, Rossing, Peter, additional, Kjaer, Andreas, additional, and Hansen, Tine Willum, additional
- Published
- 2023
- Full Text
- View/download PDF
10. Increased Subclinical Coronary Artery Pathology in Type 2 Diabetes With Albuminuria.
- Author
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Bull Rasmussen, Ida Kirstine, Skriver-Moeller, Anne-Cathrine, Ripa, Rasmus Sejersten, Hasbak, Philip, Wasehuus, Victor Soendergaard, Hadji-Turdeghal, Katra, Zobel, Emilie Hein, Lassen, Martin Lyngby, Holmvang, Lene, Slomka, Piotr, Rossing, Peter, Kjaer, Andreas, and Hansen, Tine Willum
- Subjects
TYPE 2 diabetes ,MUCOCUTANEOUS lymph node syndrome ,CORONARY arteries ,POSITRON emission tomography ,ALBUMINURIA ,DISEASE risk factors - Abstract
Diabetes affects the kidneys, and the presence of albuminuria reflects widespread vascular damage and is a risk factor for cardiovascular disease (CVD). Still, the pathophysiological association between albuminuria and CVD remains incompletely understood. Recent advances in noninvasive imaging enable functional assessment of coronary artery pathology and present an opportunity to explore the association between albuminuria and CVD. In this cross-sectional study, we evaluated the presence of subclinical coronary artery pathology in people with type 2 diabetes, free of overt CVD. Using multimodal imaging, we assessed the coronary microcalcification activity (
18 F-sodium fluoride positron emission tomography/computed tomography [PET/CT], plaque inflammation [64 Cu-DOTATATE PET/CT], and myocardial flow reserve [82 Rb PET/CT]). The study population consisted of 90 participants, stratified by albuminuria; 60 had historic or current albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g]), and 30 had normoalbuminuria (UACR <30 mg/g). We demonstrated that any albuminuria (historic or current) was associated with a more severe phenotype, in particular, higher levels of microcalcifications and impaired myocardial microvascular function; however, coronary inflammation activity was similar in people with and without albuminuria. Our findings establish a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome. Article Highlights: We undertook this study to explore the pathophysiological association between albuminuria and CVD. We wanted to answer the specific question of whether albuminuria is related to a more severe phenotype of subclinical coronary pathology. We found that albuminuria was associated with higher levels of coronary microcalcification activity and impaired myocardial microvascular function. The implications of our findings are that this establishes a potential underlying mechanism connecting cardiovascular and kidney diseases and could indicate the initial stages of the cardiorenal syndrome. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
11. Ceramides are decreased after liraglutide treatment in people with type 2 diabetes:a post hoc analysis of two randomized clinical trials
- Author
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Wretlind, Asger, Curovic, Viktor Rotbain, de Zawadzki, Andressa, Suvitaival, Tommi, Xu, Jin, Zobel, Emilie Hein, von Scholten, Bernt Johan, Ripa, Rasmus Sejersten, Kjaer, Andreas, Hansen, Tine Willum, Vilsbøll, Tina, Vestergaard, Henrik, Rossing, Peter, Legido-Quigley, Cristina, Wretlind, Asger, Curovic, Viktor Rotbain, de Zawadzki, Andressa, Suvitaival, Tommi, Xu, Jin, Zobel, Emilie Hein, von Scholten, Bernt Johan, Ripa, Rasmus Sejersten, Kjaer, Andreas, Hansen, Tine Willum, Vilsbøll, Tina, Vestergaard, Henrik, Rossing, Peter, and Legido-Quigley, Cristina
- Abstract
Background: Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of CVD. Reducing lipotoxic lipids with an antidiabetic drug therapy could be a path towards precision medicine approaches for the treatment of complications to diabetes. In this post-hoc study, an investigation was carried out on the effect of liraglutide on CVD-risk associated ceramides in two randomized clinical trials including participants with type 2 diabetes (T2D). Methods: This study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1.8 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses. Results: In the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer (p < 0.05) compared to placebo. None of the remaining ceramides showed statistically significant changes in response to liraglutide treatment compared to placebo. Significant changes in ceramides were not found after 12-weeks of liraglutide treatment in the LirAlbu12 trial. Mediation analyses show
- Published
- 2023
12. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 and [64Cu]Cu-DOTATATE PET Predict Improvement in Ischemic Cardiomyopathy
- Author
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Follin, Bjarke, Hoeeg, Cecilie, Hunter, Ingrid, Bentsen, Simon, Juhl, Morten, Jensen, Jacob Kildevang, Binderup, Tina, Nielsen, Carsten Haagen, Ripa, Rasmus Sejersten, Kastrup, Jens, Ekblond, Annette, Kjaer, Andreas, Follin, Bjarke, Hoeeg, Cecilie, Hunter, Ingrid, Bentsen, Simon, Juhl, Morten, Jensen, Jacob Kildevang, Binderup, Tina, Nielsen, Carsten Haagen, Ripa, Rasmus Sejersten, Kastrup, Jens, Ekblond, Annette, and Kjaer, Andreas
- Abstract
An increasing number of patients are living with chronic ischemic cardiomyopathy (ICM) and/or heart failure. Treatment options and prognostic tools are lacking for many of these patients. Our aim was to investigate the prognostic value of imaging angiogenesis and macrophage activation via positron emission tomography (PET) in terms of functional improvement after cell therapy. Myocardial infarction was induced in rats. Animals were scanned with [18F]FDG PET and echocardiography after four weeks and randomized to allogeneic adipose tissue-derived stromal cells (ASCs, n = 18) or saline (n = 9). Angiogenesis and macrophage activation were assessed before and after treatment by [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE. There was no overall effect of the treatment. Rats that improved left ventricular ejection fraction (LVEF) had higher uptake of both [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE at follow-up (p = 0.006 and p = 0.008, respectively). The uptake of the two tracers correlated with each other (r = 0.683, p = 0.003 pre-treatment and r = 0.666, p = 0.004 post-treatment). SUVmax at follow-up could predict improvement in LVEF (p = 0.016 for [68Ga]Ga-RGD and p = 0.045 for [64Cu]Cu-DOTATATE). High uptake of [68Ga]Ga-RGD and [64Cu]Cu-DOTATATE PET after injection of ASCs or saline preceded improvement in LVEF. The use of these tracers could improve the monitoring of heart failure patients in treatment.
- Published
- 2023
13. In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes:A cross-sectional 68Ga-RGD-PET study
- Author
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Laursen, Jens Christian, Rasmussen, Ida Kirstine Bull, Zobel, Emilie Hein, Hasbak, Philip, Holmvang, Lene, Hansen, Christian Stevns, von Scholten, Bernt Johan, Frimodt-Moller, Marie, Rossing, Peter, Hansen, Tine Willum, Kjaer, Andreas, Ripa, Rasmus Sejersten, Laursen, Jens Christian, Rasmussen, Ida Kirstine Bull, Zobel, Emilie Hein, Hasbak, Philip, Holmvang, Lene, Hansen, Christian Stevns, von Scholten, Bernt Johan, Frimodt-Moller, Marie, Rossing, Peter, Hansen, Tine Willum, Kjaer, Andreas, and Ripa, Rasmus Sejersten
- Abstract
Aims To assess cardiac angiogenesis in type 2 diabetes by positron emission tomography (PET) tracer [Ga-68]Ga-NODAGA-E[(cRGDyK)](2) (Ga-68-RGD) imaging. Methods Cross-sectional study including 20 persons with type 2 diabetes and 10 non-diabetic controls (CONs). Primary prespecified outcome was difference in cardiac angiogenesis (cardiac Ga-68-RGD mean target-to-background ratio [TBRmean]) between type 2 diabetes and CONs. Secondary outcome was to investigate associations between cardiac angiogenesis and kidney function and other risk factors. Results Participants with type 2 diabetes had a mean +/- SD age of 61 +/- 9 years, 30% were women, median (IQR) diabetes duration of 11 (6-19) years and 3 (15%) had a history of cardiovascular disease. The CONs had comparable age and sex distribution to the participants with type 2 diabetes, and none had a history of coronary artery disease. Myocardial flow reserve was lower in type 2 diabetes (2.7 +/- 0.6) compared with CONs (3.4 +/- 1.2) ( p = 0.03) and coronary artery calcium score was higher (562 [142-905] vs. 1 [0-150] p = 0.04). Cardiac Ga-68-RGD TBRmean was similar in participants with type 2 diabetes (0.89 +/- 0.09) and CONs (0.89 +/- 0.10) ( p = 0.92). Cardiac Ga-68-RGD TBRmean was not associated with estimated glomerular filtration rate, urine albumin creatinine ratio, cardiovascular disease, coronary artery calcium score or baroreflex sensitivity, neither in pooled analyses nor in type 2 diabetes. Conclusions Cardiac angiogenesis, evaluated with Ga-68-RGD PET, was similar in type 2 diabetes and CONs. Cardiac angiogenesis was not associated with kidney function or other risk markers in pooled analyses or in analyses restricted to type 2 diabetes.
- Published
- 2023
14. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure.
- Author
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Bentsen, Simon, Jensen, Jacob Kildevang, Christensen, Esben, Petersen, Lars Ringgaard, Grandjean, Constance Eline, Follin, Bjarke, Madsen, Johanne Straarup, Christensen, Camilla, Clemmensen, Andreas, Binderup, Tina, Hasbak, Philip, Ripa, Rasmus Sejersten, and Kjaer, Andreas
- Abstract
Background: Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin α
v β3 is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [68 Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. Methods: First, the real-time interaction between [68 Ga]Ga-RGD and integrin αv β3 was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [68 Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [68 Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. Results: SPR showed that [68 Ga]Ga-RGD has a high affinity for integrin αv β3 , forming a strong and stable binding. PET/CT showed a significantly higher uptake of [68 Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [68 Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. Conclusion: This study demonstrates that [68 Ga]Ga-RGD has a high affinity for integrin αv β3 , which enables the evaluation of angiogenesis and remodeling. The [68 Ga]Ga-RGD uptake after one week indicates that [68 Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
15. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 and [64Cu]Cu-DOTATATE PET Predict Improvement in Ischemic Cardiomyopathy
- Author
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Follin, Bjarke, primary, Hoeeg, Cecilie, additional, Hunter, Ingrid, additional, Bentsen, Simon, additional, Juhl, Morten, additional, Jensen, Jacob Kildevang, additional, Binderup, Tina, additional, Nielsen, Carsten Haagen, additional, Ripa, Rasmus Sejersten, additional, Kastrup, Jens, additional, Ekblond, Annette, additional, and Kjaer, Andreas, additional
- Published
- 2023
- Full Text
- View/download PDF
16. In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross‐sectional68 Ga‐RGD‐PETstudy
- Author
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Laursen, Jens Christian, primary, Rasmussen, Ida Kirstine Bull, additional, Zobel, Emilie Hein, additional, Hasbak, Philip, additional, Holmvang, Lene, additional, Hansen, Christian Stevns, additional, von Scholten, Bernt Johan, additional, Frimodt‐Møller, Marie, additional, Rossing, Peter, additional, Hansen, Tine Willum, additional, Kjaer, Andreas, additional, and Ripa, Rasmus Sejersten, additional
- Published
- 2022
- Full Text
- View/download PDF
17. Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes:A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial
- Author
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Wretlind, Asger, Zobel, Emilie Hein, De Zawadzki, Andressa, Ripa, Rasmus Sejersten, Curovic, Viktor Rotbain, Von Scholten, Bernt Johan, Mattila, Ismo Matias, Hansen, Tine Willum, Kjær, Andreas, Vestergaard, Henrik, Rossing, Peter, Legido-Quigley, Cristina, Wretlind, Asger, Zobel, Emilie Hein, De Zawadzki, Andressa, Ripa, Rasmus Sejersten, Curovic, Viktor Rotbain, Von Scholten, Bernt Johan, Mattila, Ismo Matias, Hansen, Tine Willum, Kjær, Andreas, Vestergaard, Henrik, Rossing, Peter, and Legido-Quigley, Cristina
- Abstract
Background: Liraglutide is a glucose-lowering medication used to treat type 2 diabetes and obesity. It is a GLP-1 receptor agonist with downstream metabolic changes beyond the incretin system, such as reducing the risk of cardiovascular complications. The understanding of these changes is critical for improving treatment outcomes. Herein, we present a post hoc experimental analysis using metabolomic phenotyping to discover molecular mecphanisms in response to liraglutide. Method: Plasma samples were obtained from The LiraFlame Study (ClinicalTrials.gov identifier: NCT03449654), a randomized double-blinded placebo-controlled clinical trial, including 102 participants with type 2 diabetes randomized to either liraglutide or placebo treatment for 26 weeks. Mass spectrometry-based metabolomics analyses were carried out on samples from baseline and the end of the trial. Metabolites (n=114) were categorized into pathways and linear mixed models were constructed to evaluate the association between changes in metabolites and liraglutide treatment. Results: We found the free fatty acid palmitoleate was significantly reduced in the liraglutide group compared to placebo (adjusted for multiple testing p-value = 0.04). The activity of stearoyl-CoA desaturase-1 (SCD1), the rate limiting enzyme for converting palmitate into palmitoleate, was found significantly downregulated by liraglutide treatment compared to placebo (p-value = 0.01). These metabolic changes have demonstrated to be linked to insulin sensitivity and cardiovascular health.
- Published
- 2022
18. Editorial: Advanced Cardiovascular Imaging in Diabetes
- Author
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Schick, Fritz, primary, Ripa, Rasmus Sejersten, additional, Hansen, Tine Willum, additional, and von Scholten, Bernt Johan, additional
- Published
- 2022
- Full Text
- View/download PDF
19. Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial
- Author
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Wretlind, Asger, primary, Zobel, Emilie Hein, additional, de Zawadzki, Andressa, additional, Ripa, Rasmus Sejersten, additional, Curovic, Viktor Rotbain, additional, von Scholten, Bernt Johan, additional, Mattila, Ismo Matias, additional, Hansen, Tine Willum, additional, Kjær, Andreas, additional, Vestergaard, Henrik, additional, Rossing, Peter, additional, and Legido-Quigley, Cristina, additional
- Published
- 2022
- Full Text
- View/download PDF
20. Feasibility of positron range correction in 82-Rubidium cardiac PET/CT
- Author
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Jensen, Malte, primary, Bentsen, Simon, additional, Clemmensen, Andreas, additional, Jensen, Jacob Kildevang, additional, Madsen, Johanne, additional, Rossing, Jonas, additional, Laier, Anna, additional, Hasbak, Philip, additional, Kjaer, Andreas, additional, and Ripa, Rasmus Sejersten, additional
- Published
- 2022
- Full Text
- View/download PDF
21. [ 68 Ga]Ga-NODAGA-E[(cRGDyK)] 2 and [ 64 Cu]Cu-DOTATATE PET Predict Improvement in Ischemic Cardiomyopathy.
- Author
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Follin, Bjarke, Hoeeg, Cecilie, Hunter, Ingrid, Bentsen, Simon, Juhl, Morten, Jensen, Jacob Kildevang, Binderup, Tina, Nielsen, Carsten Haagen, Ripa, Rasmus Sejersten, Kastrup, Jens, Ekblond, Annette, and Kjaer, Andreas
- Subjects
COPPER ,POSITRON emission tomography ,CARDIOMYOPATHIES ,PROGNOSIS ,VENTRICULAR ejection fraction - Abstract
An increasing number of patients are living with chronic ischemic cardiomyopathy (ICM) and/or heart failure. Treatment options and prognostic tools are lacking for many of these patients. Our aim was to investigate the prognostic value of imaging angiogenesis and macrophage activation via positron emission tomography (PET) in terms of functional improvement after cell therapy. Myocardial infarction was induced in rats. Animals were scanned with [
18 F]FDG PET and echocardiography after four weeks and randomized to allogeneic adipose tissue-derived stromal cells (ASCs, n = 18) or saline (n = 9). Angiogenesis and macrophage activation were assessed before and after treatment by [68 Ga]Ga-RGD and [64 Cu]Cu-DOTATATE. There was no overall effect of the treatment. Rats that improved left ventricular ejection fraction (LVEF) had higher uptake of both [68 Ga]Ga-RGD and [64 Cu]Cu-DOTATATE at follow-up (p = 0.006 and p = 0.008, respectively). The uptake of the two tracers correlated with each other (r = 0.683, p = 0.003 pre-treatment and r = 0.666, p = 0.004 post-treatment). SUVmax at follow-up could predict improvement in LVEF (p = 0.016 for [68 Ga]Ga-RGD and p = 0.045 for [64 Cu]Cu-DOTATATE). High uptake of [68 Ga]Ga-RGD and [64 Cu]Cu-DOTATATE PET after injection of ASCs or saline preceded improvement in LVEF. The use of these tracers could improve the monitoring of heart failure patients in treatment. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
22. In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross‐sectional 68 Ga‐RGD‐PET study.
- Author
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Laursen, Jens Christian, Rasmussen, Ida Kirstine Bull, Zobel, Emilie Hein, Hasbak, Philip, Holmvang, Lene, Hansen, Christian Stevns, von Scholten, Bernt Johan, Frimodt‐Møller, Marie, Rossing, Peter, Hansen, Tine Willum, Kjaer, Andreas, and Ripa, Rasmus Sejersten
- Subjects
KIDNEY physiology ,GLOMERULAR filtration rate ,MOLECULAR diagnosis ,IN vivo studies ,NEOVASCULARIZATION ,CROSS-sectional method ,CARDIOVASCULAR diseases ,DIAGNOSTIC imaging ,TYPE 2 diabetes ,POSITRON emission tomography ,DISEASE duration ,DESCRIPTIVE statistics ,DISEASE complications - Abstract
Aims: To assess cardiac angiogenesis in type 2 diabetes by positron emission tomography (PET) tracer [68Ga]Ga‐NODAGA‐E[(cRGDyK)]2 (68Ga‐RGD) imaging. Methods: Cross‐sectional study including 20 persons with type 2 diabetes and 10 non‐diabetic controls (CONs). Primary prespecified outcome was difference in cardiac angiogenesis (cardiac 68Ga‐RGD mean target‐to‐background ratio [TBRmean]) between type 2 diabetes and CONs. Secondary outcome was to investigate associations between cardiac angiogenesis and kidney function and other risk factors. Results: Participants with type 2 diabetes had a mean ± SD age of 61 ± 9 years, 30% were women, median (IQR) diabetes duration of 11 (6–19) years and 3 (15%) had a history of cardiovascular disease. The CONs had comparable age and sex distribution to the participants with type 2 diabetes, and none had a history of coronary artery disease. Myocardial flow reserve was lower in type 2 diabetes (2.7 ± 0.6) compared with CONs (3.4 ± 1.2) (p = 0.03) and coronary artery calcium score was higher (562 [142–905] vs. 1 [0–150] p = 0.04). Cardiac 68Ga‐RGD TBRmean was similar in participants with type 2 diabetes (0.89 ± 0.09) and CONs (0.89 ± 0.10) (p = 0.92). Cardiac 68Ga‐RGD TBRmean was not associated with estimated glomerular filtration rate, urine albumin creatinine ratio, cardiovascular disease, coronary artery calcium score or baroreflex sensitivity, neither in pooled analyses nor in type 2 diabetes. Conclusions: Cardiac angiogenesis, evaluated with 68Ga‐RGD PET, was similar in type 2 diabetes and CONs. Cardiac angiogenesis was not associated with kidney function or other risk markers in pooled analyses or in analyses restricted to type 2 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
23. Early Detection of Cardiotoxicity Using [64Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure
- Author
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Hoeeg, Cecilie, Follin, Bjarke, Grandjean, Constance Eline, Ripa, Rasmus Sejersten, Ekblond, Annette, Kastrup, Jens, Binderup, Tina, and Kjaer, Andreas
- Abstract
Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [64Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography–computed tomography ([64Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure. Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg of DOX or left untreated. Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week 8. [64Cu]Cu-RGD PET/CT scans were performed in week 4. DOX treatment led to a decline in pump function as well as an increase in cardiac and thymic uptake of [64Cu]Cu-RGD. In addition, DOX altered cardiac gene expression, led to infiltration of immune cells, reduced endothelial content, and increased interstitial fibrosis. Furthermore, concentrations of inflammatory plasma proteins were increased in the DOX group. In conclusion, DOX treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted a low left ventricular ejection fraction in week 8.
- Published
- 2024
- Full Text
- View/download PDF
24. Effect of Alirocumab on Carotid Inflammation by [ 18 F]FDG PET in Patients With Acute Myocardial Infarction.
- Author
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Bang LE, Jensen JK, Räber L, Koskinas KC, Bär S, Losdat S, Matter CM, Lonborg J, Radu Juul Jensen MD, Kjaer A, Engstrøm T, and Ripa RS
- Subjects
- Humans, Treatment Outcome, Male, Female, Aged, PCSK9 Inhibitors, Middle Aged, Positron-Emission Tomography, Myocardial Infarction diagnostic imaging, Myocardial Infarction drug therapy, Positron Emission Tomography Computed Tomography, Anti-Inflammatory Agents therapeutic use, Arteritis diagnostic imaging, Arteritis drug therapy, Proprotein Convertase 9, Fluorodeoxyglucose F18 administration & dosage, Radiopharmaceuticals administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Predictive Value of Tests, Carotid Artery Diseases diagnostic imaging, Carotid Artery Diseases drug therapy, Carotid Artery Diseases complications
- Published
- 2024
- Full Text
- View/download PDF
25. Detection of infective endocarditis with [ 64 Cu]Cu-DOTATATE positron emission tomography/computed tomography: a case series.
- Author
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Hadji-Turdeghal K, Fosbøl MØ, Hasbak P, Kjaer A, Køber L, Ripa RS, and Fosbøl EL
- Abstract
Background: Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[
18 F]fluoro-D-glucose positron emission tomography/computed tomography ([18 F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64 Cu]Cu-DOTATATE ([64 Cu]Cu-[1,4,7,10-tetraazacyclododecane- N , N ', N ″, N ‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate)., Case Summary: An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64 Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64 Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis., Discussion: In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64 Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake., Competing Interests: Conflict of interest: K.H.-T., M.Ø.F., P.H., and R.S.R.: none declared. A.K.: inventor/holds IPR on a patent covering [64Cu]Cu-DOTATATE for use in neuroendocrine tumours. L.K. has received lecture fees from Astra Zeneca, Bayer, Boehringer, Novartis, and Novo, unrelated to this manuscript. E.F. has received independent research grant related to valvular heart disease and endocarditis from the Novo Nordisk Foundation and the Danish Heart Association, unrelated to this manuscript., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)- Published
- 2024
- Full Text
- View/download PDF
26. Early Detection of Cardiotoxicity Using [ 64 Cu]Cu-NODAGA-E[(cRGDyK)]2 PET Imaging in a Rat Model of Doxorubicin-Induced Heart Failure.
- Author
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Hoeeg C, Follin B, Grandjean CE, Ripa RS, Ekblond A, Kastrup J, Binderup T, and Kjaer A
- Subjects
- Animals, Rats, Male, Heterocyclic Compounds, 1-Ring, Cardiotoxicity etiology, Acetates chemistry, Magnetic Resonance Imaging methods, Positron-Emission Tomography methods, Heart drug effects, Heart diagnostic imaging, Radiopharmaceuticals, Doxorubicin adverse effects, Doxorubicin toxicity, Heart Failure chemically induced, Heart Failure diagnostic imaging, Copper Radioisotopes, Rats, Inbred Lew, Positron Emission Tomography Computed Tomography methods, Disease Models, Animal
- Abstract
Doxorubicin (DOX) is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic effects and the lack of methods to detect these at early time points. In the present study, we evaluated if [
64 Cu]Cu-NODAGA-E[(cRGDyK)]2 positron emission tomography-computed tomography ([64 Cu]Cu-RGD PET/CT) could detect cardiotoxicity in a rat model of DOX-induced heart failure. Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg of DOX or left untreated. Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week 8. [64 Cu]Cu-RGD PET/CT scans were performed in week 4. DOX treatment led to a decline in pump function as well as an increase in cardiac and thymic uptake of [64 Cu]Cu-RGD. In addition, DOX altered cardiac gene expression, led to infiltration of immune cells, reduced endothelial content, and increased interstitial fibrosis. Furthermore, concentrations of inflammatory plasma proteins were increased in the DOX group. In conclusion, DOX treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64 Cu]Cu-RGD PET/CT at early time points. [64 Cu]Cu-RGD uptake in the myocardial septum and thymus predicted a low left ventricular ejection fraction in week 8.- Published
- 2024
- Full Text
- View/download PDF
27. In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross-sectional 68 Ga-RGD-PET study.
- Author
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Laursen JC, Rasmussen IKB, Zobel EH, Hasbak P, Holmvang L, Hansen CS, von Scholten BJ, Frimodt-Møller M, Rossing P, Hansen TW, Kjaer A, and Ripa RS
- Subjects
- Humans, Female, Middle Aged, Aged, Male, Cross-Sectional Studies, Calcium, Positron-Emission Tomography methods, Oligopeptides, Molecular Imaging, Gallium Radioisotopes, Diabetes Mellitus, Type 2 complications, Cardiovascular Diseases complications
- Abstract
Aims: To assess cardiac angiogenesis in type 2 diabetes by positron emission tomography (PET) tracer [
68 Ga]Ga-NODAGA-E[(cRGDyK)]2 (68 Ga-RGD) imaging., Methods: Cross-sectional study including 20 persons with type 2 diabetes and 10 non-diabetic controls (CONs). Primary prespecified outcome was difference in cardiac angiogenesis (cardiac68 Ga-RGD mean target-to-background ratio [TBRmean ]) between type 2 diabetes and CONs. Secondary outcome was to investigate associations between cardiac angiogenesis and kidney function and other risk factors., Results: Participants with type 2 diabetes had a mean ± SD age of 61 ± 9 years, 30% were women, median (IQR) diabetes duration of 11 (6-19) years and 3 (15%) had a history of cardiovascular disease. The CONs had comparable age and sex distribution to the participants with type 2 diabetes, and none had a history of coronary artery disease. Myocardial flow reserve was lower in type 2 diabetes (2.7 ± 0.6) compared with CONs (3.4 ± 1.2) ( p = 0.03) and coronary artery calcium score was higher (562 [142-905] vs. 1 [0-150] p = 0.04). Cardiac68 Ga-RGD TBRmean was similar in participants with type 2 diabetes (0.89 ± 0.09) and CONs (0.89 ± 0.10) ( p = 0.92). Cardiac68 Ga-RGD TBRmean was not associated with estimated glomerular filtration rate, urine albumin creatinine ratio, cardiovascular disease, coronary artery calcium score or baroreflex sensitivity, neither in pooled analyses nor in type 2 diabetes., Conclusions: Cardiac angiogenesis, evaluated with68 Ga-RGD PET, was similar in type 2 diabetes and CONs. Cardiac angiogenesis was not associated with kidney function or other risk markers in pooled analyses or in analyses restricted to type 2 diabetes., (© 2022 Diabetes UK.)- Published
- 2023
- Full Text
- View/download PDF
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