Refine
Has Fulltext
- yes (175)
Is part of the Bibliography
- yes (175)
Year of publication
Document Type
- Journal article (175) (remove)
Language
- English (175)
Keywords
- PET (22)
- positron emission tomography (21)
- prostate cancer (16)
- Positronen-Emissions-Tomografie (15)
- theranostics (14)
- CXCR4 (13)
- PET/CT (12)
- PRRT (10)
- multiple myeloma (10)
- PSMA (9)
- dosimetry (8)
- neuroendocrine tumor (8)
- radioligand therapy (8)
- SPECT (7)
- molecular imaging (6)
- 53BP1 (5)
- chemokine receptor (5)
- FDG (4)
- NET (4)
- Parkinson’s disease (4)
- SSTR (4)
- biokinetics (4)
- inflammation (4)
- lymphoma (4)
- medicine (4)
- norepinephrine transporter (4)
- radiotherapy (4)
- somatostatin receptor (4)
- sympathetic nervous system (4)
- γ-H2AX (4)
- 18F-FDG (3)
- 18F-FDG PET/CT (3)
- MRI (3)
- RADS (3)
- adrenocortical carcinoma (3)
- dopamine (3)
- imaging (3)
- machine learning (3)
- peptide receptor radionuclide therapy (3)
- prostate-specific membrane antigen (3)
- prostate-specific membrane antigen (PSMA) (3)
- radioiodine therapy (3)
- radionuclide therapy (3)
- salvage radiotherapy (3)
- 123I-mIBG (2)
- 123I-metaiodobenzylguanidine (2)
- 177Lu (2)
- 18F-FDS (2)
- 18F-LMI1195 (2)
- C-X-C motif chemokine receptor 4 (2)
- DNA damage (2)
- DNA repair (2)
- DOTATOC (2)
- FDG PET/CT (2)
- MAG3 (2)
- MIBG (2)
- Oncology (2)
- PSMA I&T (2)
- PSMA-RADS (2)
- Parkinson's disease (2)
- Positron emission tomography (2)
- Prostate Cancer (2)
- Radionuclide Therapy (2)
- SPECT/CT (2)
- SUV (2)
- Thyroid cancer (2)
- [68Ga]PentixaFor (2)
- antidepressant (2)
- biodosimetry (2)
- biomarkers (2)
- bone disease (2)
- brain (2)
- cancer (2)
- cancer treatment (2)
- cardiac (2)
- cardiac innervation imaging (2)
- cardiac nerve (2)
- children (2)
- diabetes (2)
- endoradiotherapy (2)
- fibroblast activation protein (2)
- glioblastoma multiforme (2)
- guidelines (2)
- heart failure (2)
- immunohistochemistry (2)
- in vivo imaging (2)
- involvement (2)
- isotopes (2)
- kidney (2)
- magnetic resonance imaging (2)
- management (2)
- medullary thyroid carcinoma (2)
- meningioma (2)
- metabolism (2)
- molecular medicine (2)
- myocardial sympathetic innervation imaging (2)
- nuclear medicine (2)
- personalized medicine (2)
- personalized treatment (2)
- positron emission tomography/computed tomography (2)
- precision medicine (2)
- prognosis (2)
- quantitative SPECT/CT (2)
- radial (2)
- radioiodine (2)
- radiopharmaceuticals (2)
- relapse (2)
- repair (2)
- reporting and data system (2)
- risk (2)
- sarcoidosis (2)
- somatostatin receptor (SSTR) (2)
- survival (2)
- thyroid cancer (2)
- tyrosine kinase inhibitor (2)
- vandetanib (2)
- 11C-HED (1)
- 11C-Hydroxyephedrine (1)
- 11C-Methionine PET/CT (1)
- 11C-hydroxyephedrine (1)
- 123I-Ioflupane (1)
- 131I (1)
- 133Ba (1)
- 177Lu SPECT/CT imaging (1)
- 18-F-fluorothymidine uptake (1)
- 18F-DCFPL (1)
- 18F-DCFPyL (1)
- 18F-flurpiridaz (1)
- 18FFBnTP (1)
- 1st International Workshop (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)
- 2015 (1)
- 223Ra (1)
- 224Ra (1)
- 3D printing (1)
- 5-Fluorouracil (1)
- 5IA-SPECT (1)
- 68Ga-DOTATATE/-TOC (1)
- 68Ga-PSMA ligand PET/CT (1)
- 68Ga-Pentixafor PET/CT (1)
- 99mTc-DTPA (1)
- <sup>18</sup>F-FDG (1)
- <sup>68</sup>Ga-Pentixafor (1)
- AI (1)
- Alzheimer’s disease (1)
- American Thyroid Association (1)
- Antibodies (1)
- Antidepressants (1)
- Arginine (1)
- B-cell lymphoma (1)
- BON-1 (1)
- BRAF mutation (1)
- BRAF(V600E) mutation (1)
- BSS directive (1)
- Barium-133 (1)
- Biokinetics (1)
- C-11-methionine pet (1)
- CD38 (1)
- CNS cancer (1)
- COVID-19 (1)
- CTCAE (1)
- CTNNB1 (1)
- CXCR4-targeting (1)
- CXCR4/SDF-1 (1)
- CXCR7 (1)
- CYP11B enzymes (1)
- Capicua transcriptional repressor (1)
- Carbon-11 (1)
- Cardiology (1)
- Cardiovascular diseases (1)
- Central venous access (1)
- Chernobyl (1)
- Conjugate arc therapy (1)
- Cushing’s disease (1)
- Cushing’s syndrome (1)
- DCGAN (1)
- DLBCL (1)
- DNA Breaks (1)
- DNA Damage Repair (1)
- DNA double-strand breaks (1)
- DOPA-responsive-dystonia (1)
- DOTA-EB-TATE (1)
- DSB damage (1)
- DSB focus substructure (1)
- DWI (1)
- DYT1 (1)
- DaTscan (1)
- Deep learning (1)
- Denoising (1)
- Diagnostic radiopharmaceuticals (1)
- Dosimetry (1)
- Drug resistance (1)
- Dystonia (1)
- E-cadherin (1)
- EANM (1)
- EANM dosage card (1)
- ECG (1)
- Effective dose (1)
- Extramedullary disease (1)
- Extraocular eye muscles (1)
- F-18-FDG PET (1)
- FAP (1)
- FAPI PET/CT (1)
- FDG-PET (1)
- FDG-PET/CT (1)
- FDG-PET/MRI (1)
- FLT-PET (1)
- FV45 (1)
- Fabry Disease (FD) (1)
- GAN (1)
- GCA (1)
- GCH1 (1)
- GI (1)
- Ga-68 (1)
- Ganglia (1)
- Gastrointestinal (1)
- Gb3 and lyso-Gb3 biomarkers (1)
- German population (1)
- Gleason score (1)
- Glomerular filtration (1)
- HFmrEF (1)
- HMDP hydroxymethylene diphosphonate (1)
- Hamburg (1)
- Heart failure (1)
- Hickman catheter (1)
- Highlights Lecture (1)
- Hodgkin-lymphoma (1)
- Hyperkalaemia (1)
- IBA-1 (1)
- ICD (1)
- Imaging pitfalls (1)
- JR11 (1)
- Journal of Nuclear Cardiology (1)
- KWIC (1)
- Lu-177 (1)
- Lutetium (1)
- Lysine (1)
- MDD (1)
- MIBG scintigraphy (1)
- MOR202 (1)
- MPI (1)
- MS-18 (1)
- Magnetresonanztomografie (1)
- Matlab (1)
- Medullärer Schilddrüsenkrebs (1)
- Merkel cell carcinoma (1)
- Metastases (1)
- Molecular Imaging (1)
- Molecular imaging (1)
- Monte Carlo (1)
- Multiple myeloma (1)
- Myeloma cells (1)
- Myelomas (1)
- Myocardial perfusion (1)
- Myocardial-perfusion SPECT (1)
- Myokarditis (1)
- NEC (1)
- NR3C1 (1)
- NVP-BGT226 (1)
- Neuroendocrine (1)
- Neuroendocrine Tumor (1)
- Neurosciences (1)
- Nierenfunktionsstörung (1)
- OPS201 (1)
- OXPHOS (1)
- P-glycoprotein expression (1)
- PET/MR systems (1)
- PMR (1)
- PSA (1)
- PSA response (1)
- PSMA PET/CT (1)
- PSMA-617 (1)
- PSMA-PET (1)
- PSMA-TV (1)
- PSMA‐617 (1)
- Parkinson disease (1)
- Parkinsonism (1)
- Parkionson's disease (1)
- Pediatric malignancy (1)
- Pentixafor (1)
- Phase-II (1)
- Physics and instrumentation (1)
- Pitfall (1)
- Port (1)
- Positron Emission Tomography (1)
- Positron-Emission Tomography (1)
- Positronenemissionstomografie (1)
- Preclinical evaluation (1)
- Primary hyperparathyroidism (pHPT) (1)
- Prostata (1)
- Prostate-cancer (1)
- QGP-1 (1)
- RLT (1)
- ROS (1)
- Ra-224 (1)
- Radiofluorine (1)
- Radioiodine Therapy (1)
- Radionuclide therapy (1)
- Radiopharmacy (1)
- Radiotracer (1)
- Radium (1)
- Raman micro-spectroscopy (1)
- Rhabdomyosarcoma (1)
- SAH (1)
- SARS-CoV-2 (1)
- SPECT Scanner (1)
- SSTR-PET (1)
- SSTR-RADS (1)
- Simvastatin (1)
- Single Molecule Localization Microscopy (SMLM) (1)
- Single-Photon-Emissions-Computertomographie (1)
- Sodium-Glucose Cotransporters (SGLTs) (1)
- Somatostatin receptor expression (1)
- Stammzelle (1)
- Standardisierung (1)
- T-shaped π-π stacking (1)
- T-shaped π–π stacking (1)
- T1rho (1)
- T1ρ (1)
- TBI (1)
- TKI (1)
- TSPO (1)
- TT\(_{1rho}\) mapping (1)
- T\(_{1P}\) dispersion (1)
- T\(_{1P}\) mapping (1)
- Targeted therapy (1)
- Technetium Tc 99m Sestamibi Rats (1)
- Thrombosis (1)
- Tracer (1)
- USP28 (1)
- USP8 (1)
- Virchow Node (1)
- WB-DW-MRI (1)
- Waldeyer’s tonsillar ring (1)
- Wnt (1)
- ZDF rats (1)
- [11C]-Choline PET/CT (1)
- [11C]-Methionine (1)
- [177Lu]-DOTATATE/-DOTATOC (1)
- [177Lu]/[90Y]PentixaTher (1)
- [177Lu]Lu-PSMA I&T (1)
- [177Lu]PentixaTher (1)
- [18F]FDG PET/CT (1)
- [18F]FDG-PET-CT (1)
- [18F]Fluorodeoxythymidine (1)
- [68Ga] (1)
- [68Ga]DOTATOC (1)
- [68Ga]Pentixafor (1)
- [90Y]PentixaTher (1)
- [99mTc]-Sestamibi scan (1)
- [\(^{223}\)Ra]RaCl\(_{2}\) (1)
- [\(^{68}\)Ga] Pentixafor (1)
- [\(^{68}\)Ga] pentixafor (1)
- [\(^{68}\)Ga]Ga-FAPI (1)
- [\(^{68}\)Ga]Pentixafor (1)
- \(^{11}\)C-Methionine-PET (1)
- \(^{11}\)C-methionine (1)
- \(^{177}\)Lu (1)
- \(^{177}\)Lu-OPS201 (1)
- \(^{18}\)F (1)
- \(^{18}\)F-DCFPyL PET/CT (1)
- \(^{18}\)F-FDG (1)
- \(^{18}\)F-FDG PET/CT (1)
- \(^{18}\)F-PSMA-1007 (1)
- \(^{18}\)F-fluorodeoxyglucose (1)
- \(^{68}\)Ga (1)
- \(^{68}\)Ga-Pentixafor (1)
- \(^{99m}\)Tc-MAG3 (1)
- abdominal lymph node metastases (1)
- absorbed dose (1)
- absorbed dose to the blood (1)
- accuracy (1)
- acute myeloid leukemia (1)
- acute renal failure (1)
- adenocarcinoma of the lung (1)
- adrenal incidentaloma (1)
- adrenocortical (1)
- adsorption (1)
- advanced stages (1)
- ageing (1)
- agreement (1)
- alpha particles (1)
- alpha-emitters (1)
- amino acids (1)
- amyloid-β (Aβ) (1)
- analysis (1)
- androgen deprivation therapy (1)
- angiogenesis (1)
- angiotensin II type 1 receptor (1)
- antagonist (1)
- anthropometric measurements (1)
- areas (1)
- arrhythmia (1)
- artificial intelligence (1)
- association (1)
- attention deficit/hyperactivity disorder (ADHD) (1)
- autoimmune thyroiditis (1)
- autologous transplantation (1)
- autoradiography (1)
- basal ganglia (1)
- base of support (1)
- benzylguanidine (1)
- beta oscillations (1)
- beta-catenin (1)
- biological dosimetry (1)
- biomarker (1)
- biosynthesis (1)
- blood (1)
- blood flow (1)
- bone marrow cells (1)
- bone-marrow (1)
- bone-targeting radiopharmaceuticals (1)
- brain metabolic alterations (1)
- brain tumors (1)
- breast cancer (1)
- buparlisib (1)
- butyrylcholinesterase (1)
- c-MYC (1)
- calcitonin (1)
- calibration (1)
- cancer associated fibroblasts (1)
- cancer of unknown primary (CUP) (1)
- cancer-associated fibroblast (1)
- carbamate (1)
- carboxylation (1)
- carcinoma (1)
- carcinoma metastases to pancreas (1)
- cardiac neurohormonal system (1)
- cardiac sympathetic nerve system (1)
- cardiac sympathetic nervous system (1)
- cardiomyocytes (1)
- cardioprotective potential (1)
- cardiovascular diseases (1)
- caudate nucleus (1)
- cell biology (1)
- cell staining (1)
- cells (1)
- cerebral gliomas (1)
- chemokine receptor-4 (1)
- childhood and adolescence (1)
- cholinergic activity (1)
- chromatin mobility (1)
- clinical diagnosis (1)
- coefficient (1)
- cognitive decline (1)
- coherence analysis (1)
- coherent anti-Stokes Raman scattering (CARS) microscopy (1)
- collagens (1)
- collimator (1)
- combination (1)
- comparability (1)
- comparison exercise (1)
- complex DNA damage (1)
- computational biology and bioinformatics (1)
- contractility (1)
- contrast agent (1)
- coronary artery disease (1)
- correction (1)
- criteria (1)
- damage (1)
- daratumumab (1)
- data analysis (1)
- delineation (1)
- dementia (1)
- depression (1)
- detection rate (1)
- diabetic cardiomyopathy (1)
- diagnostic medical radiation exposure (1)
- diagnostics (1)
- differentiated thyroid cancer (1)
- differentiated thyroid carcinoma (1)
- diffuse (1)
- diffusion weighted MRI (1)
- diffusion weighted mri (1)
- dilated cardiomyopathy with ataxia (1)
- disease (1)
- dissection (1)
- distant metastases (1)
- dopamine acetylcholine (1)
- dopamine transporter (DAT) (1)
- dose response (1)
- double-stranded (1)
- drug discovery (1)
- early response (1)
- editorial (1)
- ejection fraction (1)
- endocrinology (1)
- enzyme kinetics (1)
- epidemiology (1)
- esophagogastric junction (1)
- evans blue (1)
- exome sequencing (1)
- experience (1)
- exposure (1)
- extracellular matrix (1)
- extramedullary hematopoiesis (1)
- fatty acid (1)
- flare phenomenon (1)
- fluorine-18 (1)
- focal (1)
- focused surgical approach (1)
- folinic acid (1)
- follicular lymphoma (1)
- follow-up (1)
- free‐breathing (1)
- gait initiation (1)
- gamma rays (1)
- gefitinib (1)
- gemcitabine (1)
- genetics (1)
- giant cell arteritis (1)
- glioblastoma (1)
- glioma (1)
- glomerular filtration rate (1)
- glucocorticoid excess (1)
- harmonization of SPECT/CT imaging (1)
- head and neck cancer (1)
- health care (1)
- healthy volunteers (1)
- heart (1)
- heart failure with mid-range ejection fraction (1)
- heart-to-mediastinum ratio (1)
- hematotoxicity (1)
- heptacellular carcinoma (1)
- hiPSC-CM (1)
- high LET irradiation (1)
- high risk (1)
- histone H2AX (1)
- humans (1)
- hypercortisolism (1)
- hyperkalemia (1)
- hypothyroidism (1)
- imaging proliferation (1)
- imaging techniques (1)
- immune check inhibitor (1)
- immune infiltration (1)
- immunostaining (1)
- improves (1)
- in vivo formation (1)
- in-vivo (1)
- induced pluripotent stem cells (1)
- inhibition (1)
- initial experience (1)
- international multicenter comparison exercise (1)
- intraindividual comparison (1)
- iodine contrast (1)
- iodine nutrition (1)
- iodine-131 (1)
- irinotecan (1)
- irradiation (1)
- isotopic labelling (1)
- kidney function (1)
- kinase inhibitor (1)
- late response (1)
- left-ventricular function (1)
- lesions (1)
- leukocytes (1)
- levodopa-induced dyskinesia (1)
- linear conversion (1)
- locally advanced disease (1)
- long-term complications (1)
- long-term outcome (1)
- lung (1)
- lung and intrathoracic tumors (1)
- lung cancer (1)
- lutetium-177 (1)
- mRNA (1)
- macrophages (1)
- macroscopic recurrence (1)
- major depressive disorder (1)
- malignancies (1)
- malignant lymphoma (1)
- mammalian target of rapamycin (1)
- mapping (1)
- matched pair (1)
- mechanisms retention (1)
- medium-sized animals (1)
- medullary thyroid cancer (1)
- metabolic tumor volume (MTV) (1)
- metabolic tumour volume (MTV) (1)
- metastasis-directed therapy (1)
- methionine (1)
- methionine pet (1)
- methylation (1)
- methylphenidate (1)
- miRNA (1)
- mice (1)
- microenvironment (1)
- microglial cells (1)
- mitochondria (1)
- molecular biology (1)
- molecular diagnostics (1)
- molecular radiotherapy (1)
- molecular radiotherapy (MRT) (1)
- motor control (1)
- mouse (1)
- movement disorders (1)
- multi-centre (1)
- multiple system atrophy (1)
- multivariate data analysis (1)
- myocardial nerve (1)
- myocardial perfusion imaging (1)
- myocarditis (1)
- nab-paclitaxel (1)
- neoadjuvant chemotherapy (1)
- nephrology (1)
- nephrotoxicity (1)
- neuroblastoma (1)
- neuroendocrine neoplasms (NEN) (1)
- neuroendocrine tumor (NET) (1)
- neuroendocrine tumors (1)
- neuroendocrine tumors (NET) (1)
- neuroinflammation (1)
- neurology (1)
- nicotinic receptors (1)
- nitrate and thyroid carcinogenesis (1)
- non-Hodgkin's lymphoma (1)
- non-hodgkins-lymphoma (1)
- nonhuman primates (1)
- nuclear cardiology (1)
- nuclear medicine therapy (1)
- oligorecurrence (1)
- ollimator (1)
- optimization (1)
- organic cation transporter (1)
- osteoporosis (1)
- other radiation exposure (atomic bombing/nuclear accidents) (1)
- outcomes research (1)
- overall survival (1)
- oxaliplatin (1)
- pancreas (1)
- pancreatic cancer (1)
- papillary (1)
- papillary thyroid carcinoma (PTC) (1)
- parathyroid adenoma (1)
- parathyroid carcinoma (1)
- pattern (1)
- pediatric patients (1)
- pediatric thyroid cancer after Chernobyl and Fukushima (1)
- pembrolizumab (1)
- peptide receptor (1)
- peptide receptor radionuclide therapy (PRRT) (1)
- performance (1)
- peripheral injury (1)
- peripheral nervous system (1)
- phaeochromocytoma (1)
- phantom (1)
- phenethylguanidine (1)
- phosphatidylinositol-3-kinase (1)
- phosphorylation (1)
- photons (1)
- pig model (1)
- pleural mesothelioma (1)
- polymyalgia rheumatica (1)
- pooled (1)
- positron-emission-tomography (1)
- post-reconstruction filtering (1)
- power-station accident (1)
- preclinical imaging (1)
- prediction (1)
- preoperative localization (1)
- primary hyperparathyroidism (1)
- prognostic value (1)
- progression (1)
- prostate-specific antigen (1)
- pulmonary imaging (1)
- quality (1)
- quantification (1)
- quantitative MRI (1)
- quantitative imaging (1)
- radiation (1)
- radiation effects (1)
- radiobiology (1)
- radiochemistry (1)
- radiogenomics (1)
- radiotracer (1)
- radiotracer kinetics (1)
- radiotracers (1)
- radium (1)
- rats (1)
- recurrence (1)
- recurrent prostate cancer (1)
- refractory (1)
- renal (1)
- renal failure (1)
- renal function (1)
- renal imaging (1)
- renal scintigraphy (1)
- renin-angiotensin system (1)
- repeat surgery (1)
- repeated surgery (1)
- reporting and data systems (1)
- response evaluation (1)
- responsivity (1)
- rising incidence of thyroid cancer (1)
- risk assessment (1)
- scanner (1)
- screening and overdiagnosis (1)
- second hit (1)
- second primary malignancy (1)
- secondary lung tumors (1)
- self‐gated (1)
- selpercatinib (1)
- sepsis (1)
- sigma-1 receptor-directed molecular imaging (1)
- signal to noise ratio (1)
- signaling pathway (1)
- simultaneous integrated boost (1)
- single photon emission computed tomography (SPECT) (1)
- single photon emission computed tomography: sympathetic nerve (1)
- skeletal (1)
- skin biopsy (1)
- skin hemagioma (1)
- small animal (1)
- small animal SPECT (1)
- small-animal imaging (1)
- smoldering myeloma (1)
- software (1)
- solid surrogate source (1)
- solid tumors (1)
- somatostatin (1)
- somatostatin receptors (1)
- sorbents (1)
- spin lock (1)
- spin-lock (1)
- spleen (1)
- split renal function (1)
- staging (1)
- standardization (1)
- standardization of SPECT/CT imaging (1)
- standardized reporting system (1)
- statin (1)
- stem cell therapy (1)
- stem cells (1)
- stem-cell research (1)
- stem-cell transplantation (1)
- stimulation (1)
- storage vesicle turnover (1)
- striatum (1)
- stroke (1)
- structure–activity relationships (1)
- subthalamic nucleus (1)
- super ultraviolet (1)
- surgery (1)
- surgical treatment (1)
- target (1)
- taxane (1)
- therapeutic medical radiation exposure (EBRT/ RAI) (1)
- therapeutic target (1)
- thyroid (1)
- thyroid carcinoma (TC) (1)
- thyroid carcinomas (1)
- total lesion PSMA (1)
- total lesion glycolysis (TLG) (1)
- total lesion methionine uptake (TLMU) (1)
- traceability of SPECT/CT imaging (1)
- tracer (1)
- trachea (1)
- transcriptome (1)
- treatment (1)
- treatment response (1)
- trial (1)
- tumor (1)
- tumor burden (1)
- tumor heterogeneity (1)
- tumor microenvironment (1)
- unilateral ureteral obstruction (1)
- urology (1)
- valsartan (1)
- various cancer diseases (1)
- vasculature (1)
- vasculitis (1)
- vemurafenib (1)
- vestibular schwannoma (1)
- wave‐CAIPI (1)
- weight drop (1)
- whole body MRI (1)
- whole-body (1)
- young females (1)
- α-Emitter (1)
- α-Particle (1)
- α-emitter (1)
- β-catenin (1)
- γ-h2ax (1)
Institute
- Klinik und Poliklinik für Nuklearmedizin (175) (remove)
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (11)
- Johns Hopkins University School of Medicine (4)
- Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany (1)
- Department of Biomedical Imaging, National Cerebral and Cardiovascular Research Center, Suita, Japan (1)
- Department of Nuclear Medicine, Kanazawa University (1)
- Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany (1)
- Department of Paediatric Radiology, Institute of Diagnostic and Interventional Radiology, Josef-Schneider-Straße 2, Wuerzburg 97080, Germany (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 Medicine (1)
(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.
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
Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis.
Case presentation
We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment.
Conclusions
E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.
Introduction
Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging.
Materials and methods
Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I.
Results
As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction.
Conclusion
This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.
Highlights
• Loss of DNAJC19's DnaJ domain disrupts cardiac mitochondrial structure, leading to abnormal cristae formation in iPSC-CMs.
• Impaired mitochondrial structures lead to an increased mitochondrial respiration, ROS and an elevated membrane potential.
• Mutant iPSC-CMs show sarcomere dysfunction and a trend to more arrhythmias, resembling DCMA-associated cardiomyopathy.
Background
Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy.
Methods
We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca\(^{2+}\) kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tv\(_{HeLa}\)).
Results
Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca\(^{2+}\) concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to β-adrenergic stimulation.
Conclusions
Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca\(^{2+}\) kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.