Refine
Has Fulltext
- yes (50)
Is part of the Bibliography
- yes (50)
Year of publication
Document Type
- Journal article (50) (remove)
Language
- English (50)
Keywords
- Positronen-Emissions-Tomografie (15)
- PET (14)
- positron emission tomography (10)
- theranostics (9)
- neuroendocrine tumor (7)
- PRRT (5)
- CXCR4 (4)
- PET/CT (4)
- prostate cancer (4)
- radioligand therapy (4)
- sympathetic nervous system (4)
- 18F-FDG (3)
- PSMA (3)
- RADS (3)
- SPECT (3)
- SSTR (3)
- inflammation (3)
- norepinephrine transporter (3)
- peptide receptor radionuclide therapy (3)
- 18F-FDS (2)
- 18F-LMI1195 (2)
- MRI (2)
- Prostate Cancer (2)
- chemokine receptor (2)
- diabetes (2)
- heart failure (2)
- kidney (2)
- machine learning (2)
- medullary thyroid carcinoma (2)
- molecular imaging (2)
- molecular medicine (2)
- myocardial sympathetic innervation imaging (2)
- personalized medicine (2)
- personalized treatment (2)
- precision medicine (2)
- prostate-specific membrane antigen (2)
- prostate-specific membrane antigen (PSMA) (2)
- somatostatin receptor (2)
- somatostatin receptor (SSTR) (2)
- tyrosine kinase inhibitor (2)
- vandetanib (2)
- 11C-HED (1)
- 11C-Hydroxyephedrine (1)
- 11C-hydroxyephedrine (1)
- 123I-Ioflupane (1)
- 123I-mIBG (1)
- 123I-metaiodobenzylguanidine (1)
- 177Lu (1)
- 18F-DCFPL (1)
- 18F-DCFPyL (1)
- 18F-flurpiridaz (1)
- 18FFBnTP (1)
- 2- deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- 2-deoxy-2-18F-fluoro-D-sorbitol (1)
- 68Ga-DOTATATE/-TOC (1)
- 99mTc-DTPA (1)
- <sup>18</sup>F-FDG (1)
- <sup>68</sup>Ga-Pentixafor (1)
- AI (1)
- Antidepressants (1)
- C-X-C motif chemokine receptor 4 (1)
- COVID-19 (1)
- CTCAE (1)
- CXCR4-targeting (1)
- Cardiovascular diseases (1)
- DCGAN (1)
- DOTATOC (1)
- DaTscan (1)
- ECG (1)
- FV45 (1)
- GAN (1)
- GCA (1)
- GI (1)
- Ganglia (1)
- Gastrointestinal (1)
- Glomerular filtration (1)
- HFmrEF (1)
- Heart failure (1)
- Imaging pitfalls (1)
- Journal of Nuclear Cardiology (1)
- MAG3 (1)
- MDD (1)
- MIBG (1)
- MPI (1)
- Magnetresonanztomografie (1)
- Medullärer Schilddrüsenkrebs (1)
- Myocardial-perfusion SPECT (1)
- Myokarditis (1)
- NEC (1)
- NET (1)
- Neuroendocrine (1)
- Neuroendocrine Tumor (1)
- Nierenfunktionsstörung (1)
- Oncology (1)
- PMR (1)
- PSMA I&T (1)
- PSMA-617 (1)
- PSMA-PET (1)
- Parkinsonism (1)
- Parkinson’s disease (1)
- Pitfall (1)
- Positron Emission Tomography (1)
- Positron-Emission Tomography (1)
- Positronenemissionstomografie (1)
- Prostata (1)
- RLT (1)
- Radiofluorine (1)
- Radionuclide Therapy (1)
- Radiotracer (1)
- SARS-CoV-2 (1)
- SPECT Scanner (1)
- SPECT/CT (1)
- SSTR-PET (1)
- SSTR-RADS (1)
- SUV (1)
- Single-Photon-Emissions-Computertomographie (1)
- Sodium-Glucose Cotransporters (SGLTs) (1)
- Stammzelle (1)
- Standardisierung (1)
- T-shaped π-π stacking (1)
- T-shaped π–π stacking (1)
- TKI (1)
- Tracer (1)
- Virchow Node (1)
- ZDF rats (1)
- [177Lu]-DOTATATE/-DOTATOC (1)
- [177Lu]/[90Y]PentixaTher (1)
- [18F]FDG PET/CT (1)
- [68Ga] (1)
- [68Ga]DOTATOC (1)
- [68Ga]PentixaFor (1)
- [68Ga]Pentixafor (1)
- [\(^{68}\)Ga]Ga-FAPI (1)
- [\(^{68}\)Ga]Pentixafor (1)
- \(^{177}\)Lu (1)
- \(^{18}\)F (1)
- \(^{18}\)F-FDG (1)
- \(^{18}\)F-fluorodeoxyglucose (1)
- \(^{68}\)Ga (1)
- ageing (1)
- angiotensin II type 1 receptor (1)
- antidepressant (1)
- artificial intelligence (1)
- biomarkers (1)
- blood flow (1)
- cardiac innervation imaging (1)
- cardiac nerve (1)
- cardiac neurohormonal system (1)
- cardiac sympathetic nerve system (1)
- cardiac sympathetic nervous system (1)
- cardiomyocytes (1)
- cardioprotective potential (1)
- combination (1)
- computational biology and bioinformatics (1)
- coronary artery disease (1)
- depression (1)
- diabetic cardiomyopathy (1)
- editorial (1)
- ejection fraction (1)
- endocrinology (1)
- endoradiotherapy (1)
- fatty acid (1)
- fibroblast activation protein (1)
- giant cell arteritis (1)
- glomerular filtration rate (1)
- heart failure with mid-range ejection fraction (1)
- hematotoxicity (1)
- hiPSC-CM (1)
- induced pluripotent stem cells (1)
- left-ventricular function (1)
- magnetic resonance imaging (1)
- major depressive disorder (1)
- matched pair (1)
- medium-sized animals (1)
- meningioma (1)
- myocardial perfusion imaging (1)
- myocarditis (1)
- nephrology (1)
- nephrotoxicity (1)
- neuroblastoma (1)
- neuroendocrine neoplasms (NEN) (1)
- neuroendocrine tumors (NET) (1)
- neurology (1)
- nonhuman primates (1)
- nuclear cardiology (1)
- pancreas (1)
- papillary thyroid carcinoma (PTC) (1)
- performance (1)
- phaeochromocytoma (1)
- polymyalgia rheumatica (1)
- quantification (1)
- radioiodine (1)
- radiotracer (1)
- radiotracer kinetics (1)
- rats (1)
- renal (1)
- renal failure (1)
- renal function (1)
- renal imaging (1)
- renal scintigraphy (1)
- renin-angiotensin system (1)
- reporting and data system (1)
- reporting and data systems (1)
- selpercatinib (1)
- sigma-1 receptor-directed molecular imaging (1)
- single photon emission computed tomography: sympathetic nerve (1)
- solid tumors (1)
- split renal function (1)
- standardization (1)
- statin (1)
- stem cell therapy (1)
- stem cells (1)
- stem-cell research (1)
- storage vesicle turnover (1)
- stroke (1)
- structure–activity relationships (1)
- thyroid carcinoma (TC) (1)
- tracer (1)
- tumor heterogeneity (1)
- unilateral ureteral obstruction (1)
- urology (1)
- valsartan (1)
- vasculature (1)
- vasculitis (1)
Institute
- Klinik und Poliklinik für Nuklearmedizin (50)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (8)
- Medizinische Klinik und Poliklinik II (8)
- Medizinische Klinik und Poliklinik I (7)
- Institut für Pharmazie und Lebensmittelchemie (4)
- Institut für Anatomie und Zellbiologie (2)
- Pathologisches Institut (2)
- Urologische Klinik und Poliklinik (2)
- Comprehensive Cancer Center Mainfranken (1)
- Institut für Pharmakologie und Toxikologie (1)
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (11)
- Johns Hopkins University School of Medicine (4)
- Department of Biomedical Imaging, National Cerebral and Cardiovascular Research Center, Suita, Japan (1)
- Department of Nuclear Medicine, Kanazawa University (1)
- Division of Medical Technology and Science, Department of Medical Physics and Engineering, Course of Health Science, Osaka University Graduate School of Medicine, Suita Japan (1)
- Institut for Molecular Biology and CMBI, Department of Genomics, Stem Cell Biology and Regenerative Medicine, Leopold-Franzens-University Innsbruck, Innsbruck, Austria (1)
- Johns Hopkins School of Medicine, Baltimore, MD, USA (1)
- Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA (1)
- Johns Hopkins University, Baltimore, MD, U.S. (1)
- Johns Hopkis School of Medicine (1)
EU-Project number / Contract (GA) number
- 701983 (23)
Purpose: We aim to provide an overview of the conventional single photon emission computed tomography (SPECT) and emerging positron emission tomography (PET) catecholamine analogue tracers for assessing myocardial nerve integrity, in particular focusing on \(^{18}\)F-labeled tracers.
Results: Increasingly, the cardiac sympathetic nervous system (SNS) is being studied by non-invasive molecular imaging approaches. Forming the backbone of myocardial SNS imaging, the norepinephrine (NE) transporter at the sympathetic nerve terminal plays a crucial role for visualizing denervated myocardium: in particular, the single-photon-emitting NE analogue \(^{123}\)I-meta-Iodobenzylguanidine (\(^{123}\)I-mIBG) has demonstrated favorable results in the identification of patients at a high risk for cardiac death. However, cardiac neuronal PET agents offer several advantages inlcuding improved spatio-temporal resolution and intrinsic quantifiability. Compared to their \(^{11}\)C-labeled counterparts with a short half-life (20.4 min), novel \(^{18}\)F-labeled PET imaging agents to assess myocardial nerve integrity have the potential to revolutionize the field of SNS molecular imaging: The longer half-life of \(^{18}\)F (109.8 min) allows for more flexibility in the study design and delivery from central cyclotron facilities to smaller hospitals may lead to further cost reduction. A great deal of progress has been made by the first in-human studies of such \(^{18}\)F-labeled SNS imaging agents. Moreover, dedicated animal platforms open avenues for further insights into the handling of radiolabeled catecholamine analogues at the sympathetic nerve terminal. Conclusions: \(^{18}\)F-labeled imaging agents demonstrate key properties for mapping cardiac sympathetic nerve integrity and might outperform current SPECT-based or \(^{11}\)C-labeled tracers in the long run.
BACKGROUND:
Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay.
MATERIAL AND METHODS:
Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F‑2‑fluoro‑2‑deoxy‑d‑glucose (\(^{18}\)F-FDG) and \(^{125}\)I‑β‑methyl‑iodophenyl‑pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively.
RESULTS:
After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM.
CONCLUSIONS:
During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
Purpose
For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine.
Procedures
A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80).
Results
Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21).
Conclusions
A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.
Purpose of Review
Statins are routinely applied in patients with coronary artery disease, as they allow significantly to reduce blood cholesterol levels. Although those drugs are endorsed by current guidelines and prescribed routinely, a substantial portion of patients are still statin-intolerant and image-piloted strategies may then be helpful to identify patients that need further intensified treatment, e.g., to initiate treatment with proprotein convertase subtilisin / kexin type 9 inhibitors (PCSK9i). In addition, it has also been advocated that statins exhibit nonlipid, cardio-protective effects including improved cardiac nerve integrity, blood flow, and anti-inflammatory effects in congestive heart failure (HF) patients.
Recent Findings
In subjects after myocardial infarction treated with statins, \(^{123}\)I-metaiodobenzylguanidine (MIBG) scintigraphy has already revealed enhanced cardiac nerve function relative to patients without statins. In addition, all of those aforementioned statin-targeted pathways in HF can be visualized and monitored using dedicated cardiac radiotracers, e.g., \(^{123}\)I-MIBG or \(^{18}\)F-AF78 (for cardiac nerve function), \(^{18}\)F-flurpiridaz (to determine coronary flow) or \(^{68}\)Ga-PentixaFor (to detect inflammation).
Summary
Statins exhibit various cardio-beneficial effects, including improvement of cardiac nerve function, blood flow, and reduction of inflammation, which can all be imaged using dedicated nuclear cardiac radiotracers. This may allow for in vivo monitoring of statin-induced cardioprotection beyond lipid profiling in HF patients.
Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure–activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer–NET interaction, whereby a T-shaped π–π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.
Background
Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT.
Materials and methods
A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared.
Results
Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [\(^{177}\)Lu]Lu-PSMA I&T and five (9.1%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89).
Conclusion
In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.