9 results on '"Schäfers, Michael"'
Search Results
2. Radioligand therapy with 177Lu-PSMA-617 of metastatic prostate cancer has already been arrived in clinical use.
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Ahmadzadehfar, Hojjat, Essler, Markus, Schäfers, Michael, and Rahbar, Kambiz
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RADIOLIGAND assay , *DIAGNOSIS , *PROSTATE cancer - Published
- 2016
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3. Radiolabeled hydroxamate-based matrix metalloproteinase inhibitors: How chemical modifications affect pharmacokinetics and metabolic stability.
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Hugenberg, Verena, Hermann, Sven, Galla, Fabian, Schäfers, Michael, Wünsch, Bernhard, Kolb, Hartmuth C., Szardenings, Katrin, Lebedev, Artem, Walsh, Joseph C., Mocharla, Vani P., Gangadharmath, Umesh B., Kopka, Klaus, and Wagner, Stefan
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MATRIX metalloproteinases , *RADIOLABELING , *PHARMACOKINETICS , *DRUG lipophilicity , *POSITRON emission tomography , *RADIOACTIVE tracers - Abstract
Introduction Dysregulated MMP expression or activation is associated with several diseases. To study MMP activity in vivo by means of PET a radiolabeled MMP inhibitor (MMPI) functioning as radiotracer has been developed by our group based on the lead structure CGS 25966. Materials and methods Aiming at the modification of the pharmacokinetics of this lipophilic model tracer a new class of MMPIs has been discovered, consisting of additional fluorinated hydrophilic substructures, such as mini- PEG and/or 1,2,3-triazole units. To identify the best candidate for further clinical applications, radiofluorinated compounds of each subgroup have been (radio) synthesized and evaluated regarding their biodistribution behavior and their metabolic stability. Results Radiosyntheses of different triazole based MMPIs could be realized using two step “click chemistry” procedures. Compared to lead structure [ 18 F]FEtO-CGS 25966 ( [ 18 F]1e , log D (exp) = 2.02, IC 50 = 2–50 nM) all selected candidates showed increased hydrophilicities and inhibition potencies (log D (exp) = 0.23–1.25, IC 50 = 0.006–6 nM). Interestingly, despite different hydrophilicities most triazole based MMPIs showed no significant differences in their in vivo biodistribution behavior and were cleared predominantly via the hepatobiliary excretion route. Biostability and metabolism studies in vitro and in vivo revealed significant higher metabolic stability for the triazole moiety compared to the benzyl ring in the lead structure. Cleavage of ethylene glycol subunits of the mini -PEG chain led to a faster metabolism of mini -PEG containing MMPIs. Conclusion The introduction of hydrophilic groups such as mini -PEG and 1,2,3-triazole units did not lead to a significant shift of the hepatobiliary elimination towards renal clearance. Particularly the introduction of mini -PEG chains led to an intense metabolic decomposition. Substitution of the benzyl moiety in lead structure 1e by a 1,2,3-trizole ring resulted in an increased metabolic stability. Therefore, the 1,2,3-triazole-1-yl-methyl substituted MMPI [ 18 F]3a was found to be the most stable candidate in this series and should be chosen for further preclinical evaluation. [ABSTRACT FROM AUTHOR]
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- 2016
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4. SP-074 - Tumor cell imaging with derivatives of Senicapoc targeting KCa3.1 channels.
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Konken, Christian, Brömmel, Kathrin, Schelhaas, Sonja, Bulk, Etmar, Schwab, Albrecht, Schäfers, Michael, and Wünsch, Bernhard
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CELL imaging - Published
- 2021
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5. Efficient synthesis of a fluorine-18 labeled biotin derivative
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Claesener, Michael, Breyholz, Hans-Jörg, Hermann, Sven, Faust, Andreas, Wagner, Stefan, Schober, Otmar, Schäfers, Michael, and Kopka, Klaus
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FLUORINE isotopes , *CHEMICAL synthesis , *BIOTIN derivatives , *RADIOCHEMISTRY , *PHARMACOKINETICS , *METHANESULFONATES - Abstract
Abstract: Introduction: The natural occurring vitamin biotin, also known as vitamin H or vitamin B7, plays a major role in various metabolic reactions. Caused by its high binding affinity to the protein avidin with a dissociation constant of about 10-15 M the biotin-avidin system was extensively examined for multiple applications. We have synthesized a fluorine-18 labeled biotin derivative [18F]4 for a potential application in positron emission tomography (PET). Methods: Mesylate precursor 3 was obtained by an efficient two-step reaction via a copper catalyzed azide-alkyne cycloaddition (CuAAC) from easily accessible starting materials. [18F]4 was successfully synthesized by a nucleophilic radiofluorination of precursor 3. A biodistribution study by means of small-animal PET imaging in wt-mice was performed and serum stability was examined. Results: Compound [18F]4 was obtained from precursor compound 3 with an average specific activity of 16GBq/μmol within 45min and a radiochemical yield of 45±5% (decay corrected). [18F]4 demonstrated only negligible decomposition in human serum. A qualitative binding study revealed the high affinity of the synthesized biotin derivative to avidin. Blocking experiments with native biotin showed that binding was site-specific. Biodistribution studies showed that [18F]4 was cleared quickly and efficiently from the body by hepatobiliary and renal elimination. Conclusion: An efficient synthesis for [18F]4 was established. In vivo characteristics were determined and demonstrated the pharmacokinetic behaviour of [18F]4. [Copyright &y& Elsevier]
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- 2012
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6. Use of gated 13N-NH3 micro-PET to examine left ventricular function in rats
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Szymanski, Mariusz K., Kruizinga, Silvana, Tio, René A., Willemsen, Antoon T.M., Schäfers, Michael A., Stegger, Lars, Dierckx, Rudi A., Hillege, Hans L., and Slart, Riemer H.J.A.
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POSITRON emission tomography , *MYOCARDIAL infarction , *CLINICAL trials , *CORONARY disease , *INFARCTION , *CARDIOGENIC shock , *LABORATORY rats - Abstract
Abstract: Introduction: Myocardial perfusion gating techniques offer the possibility of measurement of left ventricular end-systolic (ESV) and end-diastolic volume (EDV) and left ventricular ejection fraction (LVEF) in clinical and preclinical trials. The aim of this study was to evaluate left ventricular volumes (LVV) and LVEF with 13N-NH3 in comparison with the reference 18F-FDG in different rat models. Methods: In this study, 18 male Wistar rats, 12 control rats and 6 rats with myocardial infarction (MI) were imaged with micro-PET. The ratswere scanned with gated 13N-NH3 and 18F-FDG sequentially for the assessment of LVV and LVEF. A validated three-dimensional segmentation algorithm was used to calculate LVV and LVEF. Results: Mean LVEF measured with 13N-NH3 was 45.6±8.9 and 75.3±9.4%, mean ESV was 0.40±0.12 and 0.14±0.11 ml, and mean EDVwas 0.53±16 and 0.75±0.18 ml for MI and control rats, respectively. Moderate to good correlations were observed between values of 13N-NH3 and 18F-FDG for calculation of ESV [r=0.80, P<.0001, standard error of estimate (SEE)=0.10], EDV (r=0.63, P=.005, SEE=0.14) and LVEF (r=0.84, P<.0001, SEE=9.5). LVEF measured with 13N-NH3 was significantly lower in MI rats in comparison to measurement with 18F-FDG (45.6±8.9 vs 54.9±9.3 %; P=.04). Conclusion: Correlations were moderate to good for the assessment of ESV, EDV and LVEF between gated 13N-NH3 and 18F-FDG. LVEF was underestimated with gated 13N-NH3 in rats with myocardial infarction. In healthy rats, LV volumes and LVEF can be measured reproducibly with either approach. [Copyright &y& Elsevier]
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- 2012
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7. Preclinical evaluation of an 18F-labelled β1-adrenoceptor selective radioligand based on ICI 89,406
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Law, Marilyn P., Wagner, Stefan, Kopka, Klaus, Renner, Christiane, Pike, Victor W., Schober, Otmar, and Schäfers, Michael
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RADIOLABELING , *ADRENERGIC receptors , *RADIOLIGAND assay , *LABORATORY rats , *TOMOGRAPHY , *HIGH performance liquid chromatography , *URINALYSIS , *CARDIAC imaging - Abstract
Abstract: Purpose: Radioligand binding studies indicate a down-regulation of myocardial β1-adrenoceptors (β1-AR) in cardiac disease which may or may not be associated with a decrease in β2-ARs. We have chosen ICI 89,406, a β1-selective AR antagonist, as the lead structure to develop new β1-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). Methods: (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N′-[4-(2-[18F]fluoro-ethoxy)-phenyl]-urea ((S)-[18F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[18F]F-ICI into adult CD1 mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. Results: The heart was visualised with PET after injection of (S)-[18F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective β-AR antagonist) injected 15 min after (S)-[18F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (β1-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[18F]F-ICI and radiometabolites accumulated in urine. Conclusions: Myocardial uptake of (S)-[18F]F-ICI after intravenous injection was mainly at sites unrelated to β1-ARs. (S)-[18F]F-ICI is not a suitable β1-selective-AR radioligand for PET. [Copyright &y& Elsevier]
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- 2010
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8. Synthesis and preliminary biological evaluation of new radioiodinated MMP inhibitors for imaging MMP activity in vivo
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Kopka, Klaus, Breyholz, Hans-Jörg, Wagner, Stefan, Law, Marilyn P., Riemann, Burkhard, Schröer, Sandra, Trub, Monika, Guilbert, Benedicte, Levkau, Bodo, Schober, Otmar, and Schäfers, Michael
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METALLOPROTEINASES , *METASTASIS , *ATHEROSCLEROSIS , *RADIOIODINATION , *PHOTON emission , *TOMOGRAPHY - Abstract
Non-invasive measurement of matrix metalloproteinase (MMP) activity in vivo is a clinical challenge in many disease processes such as inflammation, tumor metastasis and atherosclerosis. Therefore, radioiodinated analogues of the non-peptidyl broad-spectrum MMP inhibitor (MMPI) CGS 27023A 1a were synthesized for non-invasive detection of MMP activity in vivo using single photon emission computed tomography (SPECT). The compounds Br-CGS 27023A 1b and HO-CGS 27023A 1d were synthesized from the amino acid D-valine and used as precursors for radioiodinated derivatives of CGS 27023A and their non-radioactive references I-CGS 27023A 1c and HO-I-CGS 27023A 1e. Radioiodination of the precursors with [123I]NaI or [125I]NaI produced the no-carrier-added MMP inhibitors [123I]I-CGS 27023A 1f, [125I]I-CGS 27023A 1g, HO-[123I]I-CGS27023A 1h, and HO-[125I]I-CGS 27023A 1i. In vitro studies showed that the non-radioactive analogues of the MMP inhibitors exhibited affinities against gelatinase A (MMP-2) and gelatinase B (MMP-9) in the nanomolar range, comparable to the parent compound CGS 27023A. In vivo biodistribution using HO-[125I]I-CGS 27023A 1i in CL57 Bl6 mice showed rapid blood and plasma clearance and low retention in normal tissues. The preliminary biological evaluation warrant further studies of these radioiodinated MMP inhibitors as potential new radiotracers for imaging MMP activity in vivo. [Copyright &y& Elsevier]
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- 2004
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9. O-11 - Specific imaging of bacterial infections with 18F-labeled maltotriose ([18F]AAX90).
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Landau, Felicitas, Axer, Alexander, Niemann, Silke, Schelhaas, Sonja, Gilmour, Ryan, Schäfers, Michael, Hermann, Sven, Konken, Christian, and Faust, Andreas
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BACTERIAL diseases - Published
- 2021
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