Hans-Jürgen Wester

Technische Universität München, München, Bavaria, Germany

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Publications (273)1157.86 Total impact

  • European Urology Supplements 11/2014; 13(5):132. DOI:10.1016/S1569-9056(14)61286-0 · 3.37 Impact Factor

  • European Urology Supplements 11/2014; 13(5):170-171. DOI:10.1016/S1569-9056(14)61382-8 · 3.37 Impact Factor
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    ABSTRACT: Purpose Carbon-11- and fluorine-18-labeled choline derivatives have been introduced as promising tracers for prostate cancer imaging. However, due to limited specificity and sensitivity, there is a need for new tracers with higher sensitivity and specificity for diagnosing prostate cancer to improve tracer uptake and enhance imaging contrast. The aim of this study was to compare the properties of [11C]choline ([11C]CHO) with S(+)-β-methyl-[11C]choline ([11C]SMC) as tracer for prostate cancer imaging in a human prostate tumor mouse xenograft model by small-animal positron emission tomography/X-ray computed tomography (PET/CT). Procedures We carried out a dual-tracer small-animal PET/CT study comparing [11C]CHO and [11C]SMC. The androgen-independent human prostate tumor cell line PC3 was implanted subcutaneously in the flanks of Naval Medical Research Institute (NMRI) (nu/nu) mice (n = 11). Mice—6 weeks post-xenograft implantation—were injected with 37 MBq [11C]CHO via the tail vein. On a separate day, the mice were injected with 37 MBq [11C]SMC. Dynamic imaging was performed for 60 min with the Inveon animal PET/CT scanner (Siemens Medical Solutions) on two separate days (randomizing the sequence of the tracers). The dynamic PET images were acquired in list mode. Regions of interest (5 × 5 × 5 mm) were placed in transaxial slices in tumor, muscle (thigh), liver, kidney, and blood. Image analysis was performed calculating tumor to muscle (T/M) ratios based on summed images as well as dynamic data. Results For [11C]SMC, the mean T/M ratio was 2.24 ± 0.56 while the corresponding mean [11C]CHO T/M ratio was 1.35 ± 0.28. The T/M ratio for [11C]SMC was significant higher compared to [11C]CHO (p
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 08/2014; 17(2). DOI:10.1007/s11307-014-0782-8 · 2.77 Impact Factor
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    ABSTRACT: Due to favourable in vivo characteristics, its high specificity and the longer half-life of 18F (109.8 min) allowing for remote-site delivery, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) has gained increased importance for molecular imaging of cerebral tumors. Consequently, the development of simple and efficient production strategies for [18F]FET could be an important step to further improve the cost-effective availability of [18F]FET in the clinical environment. In the present study [18F]FET was synthesized via direct nucleophilic synthesis using an earlier developed chiral precursor, the NiII complex of an alkylated (S)-tyrosine Schiff base, Ni-(S)-BPB-(S)-Tyr-OCH2CH2OTs. The purification method has been developed via solid phase extraction thereby omitting cumbersome HPLC purification. The suggested SPE purification using combination of reverse phase and strong cation exchange cartridges provided [18F]FET in high chemical, radiochemical and enantiomeric purity and 35 % radiochemical yield (decay-corrected, 45 min synthesis time). The method was successfully automated using a commercially available synthesis module, Scintomics Hotboxone. Based on the current results, the proposed production route appears to be well suited for transfer into an automated cassette-type radiosynthesizers without using HPLC.
    Journal of Radioanalytical and Nuclear Chemistry 08/2014; 301(2):505-512. DOI:10.1007/s10967-014-3121-2 · 1.03 Impact Factor
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    International Journal of Urology 07/2014; 21(12). DOI:10.1111/iju.12577 · 2.41 Impact Factor
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    ABSTRACT: Purpose: 68Ga-labelled compounds are increasingly used for somatostatin-receptor scintigraphy because of their favourable biokinetic properties, a higher tumour-to-background contrast and higher diagnostic accuracy compared to the gamma-emitting tracer 111In-DTPA-octreotide. Recently, we have introduced the new tracer 68Ga-DOTA-3-iodo-Tyr3-Thr8-octreotide (68Ga-HA-DOTATATE). The present study demonstrates the biodistribution and radiation dosimetry of this tracer in humans. Patients, methods: Seven men were enrolled in this analysis. Every patient underwent a 20 min dynamic PET scan after intravenous injection of about 114 ± 9 MBq of 68Ga-HA-DOTATATE. This was followed by two whole-body scans at 30 min p. i. and 120 min p. i. Blood radioactivity concentration was determined non-invasively from a ROI drawn over the aorta. Urine was collected until the time of the last scan. Liver, spleen, kidneys and urinary bladder wall were included in the dosimetric estimation that was carried out with the software package OLINDA 1.0. Results: Physiological 68Ga-HA-DOTATATE uptake was observed in the pituitary gland, thyroid, salivary glands, liver, spleen, kidneys, urinary bladder, adrenals and intestine. Organs with the highest absorbed dose were spleen (0.26 ± 0.11 mSv/MBq), kidneys (0.14 ± 0.03 mSv/MBq) and liver (0.12 ± 0.02 mSv/MBq).The estimated effective dose was 0.024 ± 0.001 mSv/MBq. Conclusion: Our study demonstrates biokinetics and radiation exposure of the 68Ga-labelled tracer HA-DOTATATE to be comparable to other 68Ga-labelled SSR analogues in clinical use.
    Nuklearmedizin 07/2014; 53(5). DOI:10.3413/Nukmed-0667-14-05 · 1.49 Impact Factor
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    ABSTRACT: Background and purpose: Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic (18)F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis. Materials and methods: Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival. Results: Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11-17.37; P < .001). Most interesting, this correlation also proved significant in the subgroup of low-grade glioma (hazard ratio, 5.347; 95% CI, 1.05-27.20; P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around "hot spots" in earlier timeframes, underlining the concept of intratumor heterogeneity. Conclusions: (18)F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.
    American Journal of Neuroradiology 06/2014; DOI:10.3174/ajnr.A3980 · 3.59 Impact Factor
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    ABSTRACT: Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.
    Oncotarget 05/2014; 5(12). DOI:10.18632/oncotarget.1990 · 6.36 Impact Factor

  • The Journal of Urology 04/2014; 191(4):e471. DOI:10.1016/j.juro.2014.02.1185 · 4.47 Impact Factor
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    The Journal of Urology 04/2014; 191(4):e475. DOI:10.1016/j.juro.2014.02.1195 · 4.47 Impact Factor

  • European Urology Supplements 04/2014; 13(1):e726. DOI:10.1016/S1569-9056(14)60715-6 · 3.37 Impact Factor
  • Jakub Simeček · Johannes Notni · Tobias G Kapp · Horst Kessler · Hans-Jürgen Wester ·
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    ABSTRACT: The αvβ3-integrin addressing cyclic pentapeptide cyclo(RGDfK) was conjugated to NOPO, 1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid], a bifunctional chelator with exceptional Gallium-68 labeling properties. NOPO-c(RGDfK) and its Ga(III)- and Cu(II)-complexes showed high affinity to αvβ3 integrin (IC50 = 0.94 ± 0.06, 1.02 ± 0.09 and 0.51 ± 0.06 nM, respectively). 68Ga-labeling of NOPO-c(RGDfK) in an automated GMP-compliant procedure was performed with near-quantitative radiochemical yield, using precursor amounts as low as 0.5 nmol (approx. 0.6 µg). 68Ga-NOPO-c(RGDfK) was obtained with high purity (>99% by radio-HPLC/TLC) and, optionally, could be produced with specific activities up to 6 TBq/µmol. M21/M21L (human melanoma with high/low αvβ3 integrin expression) xenografted athymic CD-1 nude mice were used for biodistribution, in vivo stability studies and PET imaging. 68Ga-NOPO-c(RGDfK) showed rapid and specific uptake in M21 tumor xenografts (2.02 ± 0.34 % ID/g at 60 min p.i.) and was found stable in vivo. Owed to its high hydrophilicity, reflected by an octanol-water distribution coefficient (logD = -4.6) which is more than one order of magnitude lower compared to respective NOTA- or DOTA analogs, 68Ga-NOPO-c(RGDfK) showed fast renal clearance from non-targeted tissues. We conclude that NOPO is a useful means to improve renal clearance of corresponding radiopharmaceuticals by increasing the polarity of its bioconjugates. Favorable labeling properties render NOPO conjugates highly recommendable for reliable routine production of 68Ga-radiopharmaceuticals in a clinical setting.
    Molecular Pharmaceutics 03/2014; 11(5). DOI:10.1021/mp5000746 · 4.38 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of αvβ3 integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models. Immunohistochemistry and Western blot were used for characterization of αvβ3 expression in murine and human PDAC. We applied IntegriSense 680 fluorescence molecular tomography, intraoperative fluorescence imaging, and (68)Ga-NODAGA-RGD PET for αvβ3 integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a(+/Cre);Kras(+/LSL-G12D);p53(LoxP/LoxP) mice. (NODAGA is 1,4,7-triazacyclononane-1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine-glycine-aspartic acid.) RESULTS: αvβ3 integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and (68)Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders. Imaging approaches targeting αvβ3 integrin expand the potential of molecular imaging for identification of αvβ3-positive PDAC with potential implications in early detection, fluorescence-guided surgery, and therapy monitoring.
    Journal of Nuclear Medicine 02/2014; 55(3). DOI:10.2967/jnumed.113.129619 · 6.16 Impact Factor
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    ABSTRACT: Purpose Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1–5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr3-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of 68Ga-DOTA-iodo-Tyr3-octreotate [68Ga-DOTA,3-iodo-Tyr3,Thr8]octreotide (68Ga-HA-DOTATATE; HA, high-affinity) compared to the established 68Ga-DOTA-Tyr3-octreotate (68Ga-DOTATATE) in vivo. Methods The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both 68Ga-HA-DOTATATE and 68Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner. Results 68Ga-HA-DOTATATE and 68Ga-DOTATATE showed comparable uptake in the liver (SUVmean 8.9 ± 2.2 vs. 9.3 ± 2.5, n.s.), renal cortex (SUVmean 13.3 ± 3.9 vs. 14.5 ± 3.7, n.s.) and spleen (SUVmean 24.0 ± 6.7 vs. 22.9 ± 7.3, n.s.). A somewhat higher pituitary uptake was found with 68Ga-HA-DOTATATE (SUVmean 6.3 ± 1.8 vs. 5.4 ± 2.1, p < 0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. 68Ga-HA-DOTATATE demonstrated 328 lesions (95.3 % of total lesions seen), and 68Ga-DOTATATE demonstrated 332 lesions (96.4 %). The mean SUVmax of all lesions was not significantly different between 68Ga-HA-DOTATATE and 68Ga-DOTATATE (17.8 ± 11.4 vs. 16.7 ± 10.7, n.s.). Conclusion Our analysis demonstrated very good concordance between 68Ga-HA-DOTATATE and 68Ga-DOTATATE PET data. As the availability and use of 68Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other 68Ga-labelled hsst analogues.
    European Journal of Nuclear Medicine 02/2014; 41(6). DOI:10.1007/s00259-014-2690-1 · 5.38 Impact Factor
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    ABSTRACT: The goal of this study was to evaluate the feasibility of [(18)F]Galacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of αvβ3 expression in human carotid plaques. The integrin αvβ3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. [(18)F]Galacto-RGD is a PET tracer binding specifically to αvβ3. Therefore, [(18)F]Galacto-RGD PET/CT imaging of αvβ3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability. [(18)F]Galacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background [TB] ratio). TB ratio was correlated with immunohistochemistry of αvβ3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with [(18)F]Galacto-RGD and competition experiments with an unlabeled αvβ3-specific RGD peptide were performed. [(18)F]Galacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with αvβ3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance. [(18)F]Galacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with αvβ3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of αvβ3 expression for assessment of plaque inflammation in patients.
    JACC. Cardiovascular imaging 01/2014; 7(2). DOI:10.1016/j.jcmg.2013.12.003 · 7.19 Impact Factor
  • Jakub Simeček · Ondřej Zemek · Petr Hermann · Johannes Notni · Hans-Jürgen Wester ·
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    ABSTRACT: The bifunctional chelator NOPO (1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid]) shows remarkably high Ga(III) complexation efficiency and comprises one carboxylic acid moiety which is not involved into metal ion coordination. An improved synthetic protocol affords NOPO with 45% overall yield. Stepwise protonation constants (log Ka), determined by potentiometry, are 11.96, 5.22, 3.77, and 1.54; the stability constant of the Ga(III) complex is log KGaL = 25.0. Within 5 min, (68)Ga(III) incorporation by NOPO is virtually quantitative at room temperature between pH 3 and 4, and at 95 °C at pH ranging from 0.5 to 7, at NOPO concentrations of 30 μM and 10 μM, respectively. During amide bond formation at the distant carboxylate using the HATU coupling reagent, an intramolecular phosphinic acid ester (phosphilactone) is formed, which is cleaved during (68)Ga complexation or in acidic media, such as trifluoroacetic acid (TFA). Phosphilactone formation can also be suppressed by complexation of Zn(2+) prior to conjugation, the resulting zinc-containing conjugates nevertheless being suitable for direct (68)Ga-labeling. In AR42J (rat pancreatic carcinoma) xenografted CD-1 nude mice, (68)Ga-labeled NOPO-NaI(3)-octreotide conjugate ((68)Ga-NOPO-NOC) showed high and fully blockable tumor uptake (13.9 ± 5% ID/g, 120 min p.i., compared to 0.9 ± 0.4% ID/g with 5 mg/kg of nonlabeled peptide). Uptake in other tissues was generally below 3% ID/g, except appearance of excretion-related activity accumulation in kidneys. NOPO-functionalized compounds tend to be more hydrophilic than the corresponding DOTA- and NODAGA-conjugates, thus promoting fast and extensive renal excretion of (68)Ga-NOPO-radiopharmaceuticals. NOPO-functionalized peptides provide suitable pharmacokinetics in vivo and meet all requirements for efficient (68)Ga-labeling even at room temperature in a kit-like manner.
    Molecular Pharmaceutics 12/2013; 11(11). DOI:10.1021/mp400642s · 4.38 Impact Factor
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    ABSTRACT: In‐vivo‐Tumorbildgebung mithilfe der Positronenemissionstomographie (PET) ist möglich nach der Funktionalisierung von α5β1‐ oder αvβ3‐selektiven Integrinantagonisten mit dem Chelatbildner NODAGA. H. Kessler et al. zeigen in der Zuschrift auf S. 11870 ff. auch, dass diese Peptidmimetika in einem Rattenaortaringtest (RAR‐Assay) die bFGF‐ und VEGF‐stimulierte Angiogenese blockieren können und Antitumorwirkung in einem Fibrosarkommodell in Mäusen haben. (Bild: Philipp Ganthaler)
    Angewandte Chemie 10/2013; 125(44). DOI:10.1002/ange.201308315
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    ABSTRACT: In vivo tumor imaging by positron emission tomography (PET) is possible following the functionalization of α5β1 or αvβ3 subtype‐selective integrin antagonists with NODAGA. H. Kessler and co‐workers also show in their Communication on page 11656 ff. that these peptidomimetics are able to block bFGF‐ and VEGF‐stimulated angiogenesis in a rat aortic ring (RAR) assay, and exert anti‐tumor effects in a fibrosarcoma model in mice. (Picture designed by Philipp Ganthaler.)
    Angewandte Chemie International Edition 10/2013; 52(44). DOI:10.1002/anie.201308315 · 11.26 Impact Factor
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    ABSTRACT: Pattern seekers: For the two angiogenic relevant integrins α5β1 and αvβ3, functionalized derivatives of the selective antagonists 1 and 2 could target and discriminate between tumor cells in vivo based on their different integrin patterns and also delay tumor growth in vivo. In addition, the first α5β1-selective integrin antagonist that enables specific molecular imaging by positron emission tomography was developed.
    Angewandte Chemie International Edition 10/2013; 52(44). DOI:10.1002/anie.201306376 · 11.26 Impact Factor
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    ABSTRACT: Diagnose und Therapie: Derivate der für die beiden angiogenetisch relevanten Integrine α5β1 und αvβ3 selektiven Antagonisten 1 bzw. 2 können Tumorzellen mit unterschiedlichen Integrinmustern in vivo selektiv ansprechen und das Tumorwachstum in vivo verzögern. Weiterhin wurde der erste α5β1‐selektive Integrinantagonist entwickelt, der die spezifische molekulare Bildgebung mit Positronenemissionstomographie ermöglicht.
    Angewandte Chemie 10/2013; 125(44). DOI:10.1002/ange.201306376

Publication Stats

9k Citations
1,157.86 Total Impact Points


  • 1999-2015
    • Technische Universität München
      • • Nuklearmedizinische Klinik und Poliklinik
      • • Section of Radiochemistry and Pharmaceutical Radiochemistry
      München, Bavaria, Germany
  • 2002-2014
    • Deutsches Herzzentrum München
      • Department of Cardiovascular Surgery
      München, Bavaria, Germany
  • 2012
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 2005
    • ATOS Klinik Munich
      Münchenbernsdorf, Thuringia, Germany
  • 1994-1996
    • Forschungszentrum Jülich
      • Institute of Neurosciences and Medicine (INM)
      Jülich, North Rhine-Westphalia, Germany