Abstract:
PURPOSE:Deposition of misfolded alpha-synuclein (αSYN) aggregates in the human brain is one of the major hallmarks of synucleinopathies. However, a target-specific tracer to detect pathological aggregates of αSYN remains lacking. Here, we report the development of a positron emission tomography (PET) tracer based on anle138b, a compound shown to have therapeutic activity in animal models of neurodegenerative diseases. METHODS:Specificity and selectivity of [3H]MODAG-001 were tested in in vitro binding assays using recombinant fibrils. After carbon-11 radiolabeling, the pharmacokinetic and metabolic profile was determined in mice. Specific binding was quantified in rats, inoculated with αSYN fibrils and using in vitro autoradiography in human brain sections of Lewy body dementia (LBD) cases provided by the Neurobiobank Munich (NBM). RESULTS:[3H]MODAG-001 revealed a very high affinity towards pure αSYN fibrils (Kd = 0.6 ± 0.1 nM) and only a moderate affinity to hTau46 fibrils (Kd = 19 ± 6.4 nM) as well as amyloid-β1-42 fibrils (Kd = 20 ± 10 nM). [11C]MODAG-001 showed an excellent ability to penetrate the mouse brain. Metabolic degradation was present, but the stability of the parent compound improved after selective deuteration of the precursor. (d3)-[11C]MODAG-001 binding was confirmed in fibril-inoculated rat striata using in vivo PET imaging. In vitro autoradiography showed no detectable binding to aggregated αSYN in human brain sections of LBD cases, most likely, because of the low abundance of aggregated αSYN against background protein. CONCLUSION:MODAG-001 provides a promising lead structure for future compound development as it combines a high affinity and good selectivity in fibril-binding assays with suitable pharmacokinetics and biodistribution properties.
journal_name
Eur J Nucl Med Mol Imagingauthors
Kuebler L,Buss S,Leonov A,Ryazanov S,Schmidt F,Maurer A,Weckbecker D,Landau AM,Lillethorup TP,Bleher D,Saw RS,Pichler BJ,Griesinger C,Giese A,Herfert Kdoi
10.1007/s00259-020-05133-xsubject
Has Abstractpub_date
2020-12-28 00:00:00eissn
1619-7070issn
1619-7089pii
10.1007/s00259-020-05133-xpub_type
杂志文章abstract:PURPOSE:Early detection of infectious endocarditis is challenging. For diagnosing infectious endocarditis, the revised Duke criteria are the gold standard. Evidence of endocardial involvement on echocardiography is a major criterion, but sensitivity and specificity of echocardiography are not optimal. Here we investiga...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-013-2376-0
更新日期:2013-07-01 00:00:00
abstract:PURPOSE:Left ventricular (LV) mechanical dyssynchrony (LVMD) was assessed by gated single-photon emission CT myocardial perfusion imaging (MPI) as an independent predictor of death from any cause in patients with known coronary artery disease (CAD) and reduced LV function. METHODS:Between 2001 and 2010, 135 patients (...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-012-2157-1
更新日期:2012-10-01 00:00:00
abstract:PURPOSE:The usefulness of (18)F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [(18)F]-3-fluoro-alpha-methyl tyrosine ((18)F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of (18)F-FAMT PET/CT to complement (18)F-FDG PET...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-013-2487-7
更新日期:2013-10-01 00:00:00
abstract::Radiomics in nuclear medicine is rapidly expanding. Reproducibility of radiomics studies in multicentre settings is an important criterion for clinical translation. We therefore performed a meta-analysis to investigate reproducibility of radiomics biomarkers in PET imaging and to obtain quantitative information regard...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章,评审
doi:10.1007/s00259-019-04391-8
更新日期:2019-12-01 00:00:00
abstract:PURPOSE:Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is commonly accepted as the gold standard to assess outcome after NAC in breast cancer patients. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has unique value in tumor staging, predicting prognosis, and eval...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-020-04684-3
更新日期:2020-05-01 00:00:00
abstract::The Annual Congress of the European Association of Nuclear Medicine represents the major scientific and professional event in the field of nuclear medicine in Europe. Specialists from all allied professions meet to discuss the latest findings and discoveries. A very large industrial exhibition demonstrates the latest ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type:
doi:10.1007/s00259-004-1720-9
更新日期:2005-01-01 00:00:00
abstract:PURPOSE:Tau pathology progression in Alzheimer's disease (AD) is explained through the network degeneration hypothesis and the neuropathological Braak stages; however, the compatibility of these models remains unclear. METHODS:We utilized [18F]AV-1451 tau-PET scans of 39 subjects with AD and 39 sex-matched amyloid-neg...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-020-05183-1
更新日期:2021-01-18 00:00:00
abstract:PURPOSE:While methods for imaging tumor hypoxia with positron emission tomography (PET) have been developed, optimal methods for interpreting and utilizing these datasets in the clinic remain unclear. In this study, we analyzed hypoxia PET images of head and neck cancer patients and compared imaging metrics with human ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-015-3247-7
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSM...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-017-3877-z
更新日期:2018-02-01 00:00:00
abstract::[Yttrium-90-DOTA-Tyr(3)]-octreotide (DOTATOC) and [(177)Lu-DOTA-Tyr(3)-Thr(8)]-octreotide (DOTATATE) are used for peptide receptor-mediated radionuclide therapy (PRMRT) in neuroendocrine tumours. No human data comparing these two compounds are available so far. We used (111)In as a surrogate for (90)Y and (177)Lu and ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-004-1553-6
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:The objective of this study was to explore the feasibility of harmonising performance for PET/CT systems equipped with time-of-flight (ToF) and resolution modelling/point spread function (PSF) technologies. A second aim was producing a working prototype of new harmonising criteria with higher contrast recoverie...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-018-3977-4
更新日期:2018-07-01 00:00:00
abstract:PURPOSE:Although [(18)F]FDG PET can measure therapy response sooner and more accurately than morphological imaging techniques, there is still some debate as to whether [(18)F]FDG uptake really reflects changes in the viable cell fraction. In this study changes in [(18)F]FDG uptake were investigated in a lymphoma model ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-010-1479-0
更新日期:2010-08-01 00:00:00
abstract:PURPOSE:The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-015-3004-y
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:In vivo Alzheimer's disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [18F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [18F]flortaucipir PET and the associations of both tau biomarkers with cognit...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-020-04758-2
更新日期:2020-11-01 00:00:00
abstract:PURPOSE:Noninvasive markers of disease activity in patients with idiopathic pulmonary fibrosis (IPF) are lacking. We performed this study to investigate the reproducibility of pulmonary (18)F-FDG PET/CT in patients with IPF. METHODS:The study group comprised 13 patients (11 men, 2 women; mean age 71.1 ± 9.9 years) wit...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-011-1986-7
更新日期:2012-03-01 00:00:00
abstract:PURPOSE:Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional alpha-[(11)C]methyl-L: -tryptophan (alpha-[(11)C]MTrp) trapping rate constant (K*; microl.g(-1).min(-1)), whi...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-007-0365-x
更新日期:2007-08-01 00:00:00
abstract:PURPOSE:Carimas (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-009-1143-8
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:The purpose of this prospective study was to evaluate the usefulness of (18)F-fluorodeoxyglucose (FDG) and (11)C-choline positron emission tomography (PET)/computed tomography (CT) for detecting recurrences of advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy. Additionall...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-010-1400-x
更新日期:2010-07-01 00:00:00
abstract:PURPOSE:The aim of this study is to report on a collective of 20 children from Belarus who had developed papillary thyroid carcinoma with pulmonary metastases after the Chernobyl disaster. In all children fractionated radioiodine therapy (RIT) was ceased before achieving complete remission due to a lack of further effe...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-010-1669-9
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:We analysed a correlation between pre- to post-treatment primary tumour metabolic volume (PT-MV) reduction on 18F-FDG-PET/CT and survival in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT). METHODS:Sixty consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), treated w...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-018-4063-7
更新日期:2018-11-01 00:00:00
abstract:PURPOSE:Brain serotonin 6 receptor (5-HT6) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-014-2936-y
更新日期:2015-03-01 00:00:00
abstract::Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three (68)Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these (68)Ga-sstr-binding peptides ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章,评审
doi:10.1007/s00259-016-3395-4
更新日期:2016-10-01 00:00:00
abstract:PURPOSE:Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-007-0635-7
更新日期:2008-04-01 00:00:00
abstract::This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-003-1413-9
更新日期:2004-04-01 00:00:00
abstract:PURPOSE:To examine the diagnostic performance of (18)F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with (18)F-fluorodeoxyglucose (FDG) PET/CT. METHODS:The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-013-2424-9
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-011-1882-1
更新日期:2011-12-01 00:00:00
abstract:PURPOSE:The aim of the present study is to prospectively evaluate the prognostic value of previously defined [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up. METHODS:Forty-two ...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-012-2229-2
更新日期:2012-12-01 00:00:00
abstract:INTRODUCTION:Fluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-(99m)Tc-nanocolloid, it has become...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-016-3372-y
更新日期:2016-09-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate whether 68Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients. METHODS:We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purpos...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-020-04981-x
更新日期:2021-02-01 00:00:00
abstract:PURPOSE:Continuous bed motion has recently been introduced for whole-body PET/CT, and represents a paradigm shift towards individualized and flexible acquisition without the limitations of bed position-based planning. Increased patient comfort due to lack of abrupt table position changes may be another albeit still unp...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00259-015-3226-z
更新日期:2016-04-01 00:00:00