Hans-Jürgen Wester

Technische Universität München, München, Bavaria, Germany

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Publications (152)739.89 Total impact

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    ABSTRACT: Expression of α(v)β(3) integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of α(v)β(3) integrin-targeted positron emission tomography tracer (18)F-galacto-RGD in mouse atherosclerotic plaques. Hypercholesterolemic LDLR(-/-) ApoB(100/100) mice on high-fat diet for 4 months were randomized to further 3 months on high-fat diet (high-fat group, n = 8) or regular mouse chow (intervention group, n = 7). Intima-media ratio describing plaque burden was comparable between intervention and high-fat groups (2.0 ± 0.5 vs 2.3 ± 0.8, P = .5). Uptake of (18)F-galacto-RGD in the aorta was lower in the intervention than high-fat group (%ID/g 0.16 vs 0.23, P < .01). Autoradiography showed 35% lower uptake of (18)F-galacto-RGD in the atherosclerotic plaques in the intervention than high-fat group (P = .007). Uptake of (18)F-galacto-RGD in plaques correlated with uptake of (3)H-deoxyglucose and nuclear density, which was lower in the intervention than high-fat group (P = .01). Flow cytometry demonstrated macrophages expressing α(v) and β(3) integrins in the aorta. Uptake of (18)F-galacto-RGD in mouse atherosclerotic lesions was reduced by lipid-lowering diet intervention. Expression of α(v)β(3) integrin is a potential target for evaluation of therapy response in atherosclerosis.
    Journal of Nuclear Cardiology 04/2012; 19(4):775-84. DOI:10.1007/s12350-012-9554-5 · 2.65 Impact Factor
  • Johannes Notni, Jan Plutnar, Hans-Jürgen Wester
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    ABSTRACT: Bisphosphonates possess strong affinity to bone. 99mTc bisphosphonate complexes are widely used for bone scintigraphy. For positron emission tomography (PET) bone imaging, Ga-68-based PET tracers based on bisphosphonates are highly desirable. Two trimeric bisphosphonate conjugates of the triazacyclononane-phosphinate (TRAP) chelator were synthesized, labeled with Ga-68, and used for microPET imaging of bone in male Lewis rats. Both Ga-68 tracers show bone uptake and, thus, are suitable for PET bone imaging. Surprisingly, Ga-71 nuclear magnetic resonance data prove that Ga(III) is not located in the chelating cavity of TRAP and must therefore be bound by the conjugated bisphosphonate units. The intrinsic Ga-68 chelating properties of TRAP are not needed for Ga-68 PET bone imaging with TRAP-bisphosphonate conjugates. Here, TRAP serves only as a trimeric scaffold. For preparation of Ga-68-based bone seekers for PET, it appears sufficient to equip branched scaffolds with multiple bisphosphonate units, which serve both Ga-68-binding and bone-targeting purposes.
    03/2012; 2(1):13. DOI:10.1186/2191-219X-2-13
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    ABSTRACT: In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [(11)C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [(11)C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [(11)C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
    PLoS ONE 03/2012; 7(3):e31310. DOI:10.1371/journal.pone.0031310 · 3.53 Impact Factor
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    ABSTRACT: (18)F-galacto-RGD ((18)F-RGD) is a PET tracer binding to α(v)β(3) integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial (18)F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with (18)F-RGD to evaluate α(v)β(3) integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by (13)N-ammonia PET and MRI, respectively. One week after MI, (18)F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 0.04, P < 0.001). At this time, (18)F-RGD uptake was associated with capillary density in histologic sections. Average (18)F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 ± 0.07 vs. 0.21 ± 0.05, P < 0.05). In a multivariable logistic regression analysis, low (18)F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). High levels of (18)F-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that α(v)β(3) integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.
    Journal of Nuclear Medicine 02/2012; 53(2):318-23. DOI:10.2967/jnumed.111.091652 · 5.56 Impact Factor
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    ABSTRACT: N-Succinimidyl 3-(di-tert-butyl[(18)F]fluorosilyl)benzoate ([(18)F]SiFB), a novel synthon for one-step labeling of proteins, was synthesized via a simple (18)F-(19)F isotopic exchange. A new labeling technique that circumvents the cleavage of the highly reactive active ester moiety under regular basic (18)F-labeling conditions was established. In order to synthesize high radioactivity amounts of [(18)F]SiFB, it was crucial to partially neutralize the potassium oxalate/hydroxide that was used to elute (18)F(-) from the QMA cartridge with oxalic acid to prevent decomposition of the active ester moiety. Purification of [(18)F]SiFB was performed by simple solid-phase extraction, which avoided time-consuming HPLC and yielded high specific activities of at least 525 Ci/mmol and radiochemical yields of 40-56%. In addition to conventional azeotropic drying of (18)F(-) in the presence of [K(+)⊂2.2.2.]C(2)O(4), a strong anion-exchange (SAX) cartridge was used to prepare anhydrous (18)F(-) for nucleophilic radio-fluorination omitting the vacuum assisted drying of (18)F(-). Using a lyophilized mixture of [K(+)⊂2.2.2.]OH resolubilized in acetonitrile, the (18)F(-) was eluted from the SAX cartridge and used directly for the [(18)F]SiFB synthesis. [(18)F]SiFB was applied to the labeling of various proteins in likeness to the most commonly used labeling synthon in protein labeling, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Rat serum albumin (RSA), apo-transferrin, a β-cell-specific single chain antibody, and erythropoietin were successfully labeled with [(18)F]SiFB in good radiochemical yields between 19% and 36%. [(18)F]SiFB- and [(18)F]SFB-derivatized RSA were directly compared as blood pool imaging agents in healthy rats using small animal positron emission tomography. Both compounds demonstrated identical biodistributions in healthy rats, accurately visualizing the blood pool with PET.
    Bioconjugate Chemistry 12/2011; 23(1):106-14. DOI:10.1021/bc200525x · 4.82 Impact Factor
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    ABSTRACT: A veritable gallium TRAP: Triazacyclononane-phosphinic acid chelators (TRAP) form highly stable complexes with Ga(3+) extremely efficiently over a wide pH range. Homo- and heteromultimeric bioconjugates can be synthesized in a straightforward manner, all of which renders TRAP a chelator with ideal properties for (68) Ga positron emission tomography (PET) imaging agent elaboration.
    Chemistry - A European Journal 12/2011; 17(52):14718-22. DOI:10.1002/chem.201103503 · 5.93 Impact Factor
  • Markus Schwaiger, Hans-Jürgen Wester
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    ABSTRACT: The recognized need for new PET tracers is associated with increases in available PET instrumentation and with unmet clinical challenges in the early diagnosis and staging of diseases. The clinical success of (18)F-FDG PET has resulted in the acceptance of biologic signals as part of disease management. The advantages of PET technology over SPECT will lead to the introduction of new PET tracers for established nuclear medicine imaging indications. Disease-specific markers such as amyloid ligands will lead to new applications of PET to neurodegenerative diseases that are prevalent in aging societies. The translation of molecular imaging to clinical applications will require combining specific tracer approaches with targeted therapy for the realization of personalized medicine. An important aspect of the introduction of new PET tracers will be the emergence of a specialized radiopharmaceutical industry and professional distribution networks. The number of available PET tracers not only will follow rules of demand and supply but also will be dependent on the regulatory environment of individual health care systems.
    Journal of Nuclear Medicine 12/2011; 52 Suppl 2:36S-41S. DOI:10.2967/jnumed.110.085738 · 5.56 Impact Factor
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    ABSTRACT: Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma. Proliferation activity is considered an important prognostic marker. Immunohistochemical analysis from core biopsy or lymph node may not represent the proliferation rate. We investigated the in vivo proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) to characterize MCL. Eight untreated MCL patients were recruited prospectively. (18)F-FLT PET/CT was performed 45 min after injection of (18)F-FLT. (18)F-FDG PET/CT served as reference. Mean (18)F-FLT standardized uptake values were assessed per lesion and compared with respective (18)F-FDG uptake. Correlation of mean (18)F-FLT and (18)F-FDG uptake in the hottest lesion to Ki67 immunostaining was performed. Five patients underwent repetitive early (18)F-FLT PET. All lymphoma lesions identified by (18)F-FDG PET/CT showed increased (18)F-FLT uptake. Semiquantitative analysis revealed a high mean (18)F-FLT standardized uptake value of 9.9 (range, 5.5-15.9). Mean (18)F-FLT uptake and Ki67 expressions showed a strong positive correlation. PET using (18)F-FLT as a biomarker for proliferative activity showed a high sensitivity for MCL. (18)F-FLT uptake shows a correlation with proliferation. Our results warrant further analysis of (18)F-FLT PET in MCL.
    Journal of Nuclear Medicine 11/2011; 52(12):1898-902. DOI:10.2967/jnumed.111.094698 · 5.56 Impact Factor
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    ABSTRACT: The overexpression of the chemokine receptor CXCR4 plays an important role in oncology, since together with its endogenous ligand, the stromal cell-derived factor (SDF1-α), CXCR4 is involved in tumor development, growth, and organ-specific metastasis. As part of our ongoing efforts to develop highly specific CXCR4-targeted imaging probes and with the aim to assess the suitability of this ligand for first proof-of-concept studies in humans, we further evaluated the new (68)Ga-labeled high-affinity cyclic CXCR4 ligand, (68)Ga-CPCR4-2 (cyclo(D-Tyr(1)-[NMe]-D-Orn(2)-[4-(aminomethyl) benzoic acid,(68)Ga-DOTA]-Arg(3)-2-Nal(4)-Gly(5))). Additional biodistribution and competitions studies in vivo, dynamic PET studies, and investigations on the metabolic stability and plasma protein binding were performed in nude mice bearing metastasizing OH1 human small cell lung cancer xenografts. CXCR4 expression on OH1 tumor sections was determined by immunohistochemical staining. (nat)Ga-CPCR4-2 exhibits high CXCR4 affinity with a half maximum inhibitory concentration of 4.99 ± 0.72 nM. (68)Ga-CPCR4-2 showed high in vivo stability and high and specific tumor accumulation, which was reduced by approximately 80% in competition studies with AMD3100. High CXCR4 expression in tumors was confirmed by immunohistochemical staining. (68)Ga-CPCR4-2 showed low uptake in nontumor tissue and particularly low kidney accumulation despite predominant renal excretion, leading to high-contrast delineation of tumors in small-animal PET studies. The small and optimized cyclic peptide CPCR4-2 labeled with (68)Ga is a suitable tracer for targeting and imaging of human CXCR4 receptor expression in vivo. The high affinity for CXCR4, its in vivo stability, and the excellent pharmacokinetics recommend the further evaluation of (68)Ga-CPCR4-2 in a proof-of-concept study in humans.
    Journal of Nuclear Medicine 11/2011; 52(11):1803-10. DOI:10.2967/jnumed.111.098798 · 5.56 Impact Factor
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    ABSTRACT: The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with excellent antagonistic activity using a derivative of a cyclic pentapeptide as monomer. To optimize the binding affinity, we investigated the influence of the distance between the monomers and the pharmacophoric sites in the synthesized constructs. The affinity studies in combination with docking computations support a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals, thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA conjugates and some of their corresponding metal complexes retain good CXCR4 affinity, and one (68)Ga labeled compound was studied as PET tracer.
    Journal of Medicinal Chemistry 09/2011; 54(21):7648-62. DOI:10.1021/jm2009716 · 5.48 Impact Factor
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    ABSTRACT: 18F-labeled imidazo[2,1-b]benzothiazole ([18F]8) was synthesized and evaluated as a tracer for cerebral β-amyloid deposits (Aβ) by means of positron emission tomography (PET). [18F]8 exhibits a high affinity to Aβ and suitable brain uptake kinetics combined with a high metabolic stability in the brain. In a double transgenic APP/PS1 mouse model of Alzheimer's disease, we demonstrated a specific uptake of [18F]8 in Aβ-containing telencephalic brain regions. The specific binding of [18F]8 to Aβ was confirmed by regional brain biodistribution and autoradiography and correlated to immunohistochemistry staining. Analysis of brain sections of APP/PS1 mouse injected with a cocktail of [18F]8 and reference compound [3H]PiB revealed that the two tracers bind to Aβ plaques in the brain of mouse in a comparable binding pattern. [18F]8 represents the first high-contrast PET imaging agent for detection of Aβ plaques in transgenic mouse model of Alzheimer's disease and holds promise for transfer to a clinical evaluation.Keywords: Alzheimer's disease; 18F-labeled tracer for β-amyloid; IBT; β-amyloid plaques; positron emission tomography; autoradiography; APP/PS1transgenic mice; neuroimaging
    ACS Medicinal Chemistry Letters 07/2011; 2(9). DOI:10.1021/ml200123w · 3.07 Impact Factor
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    ABSTRACT: Neuroendocrine tumours are frequently located in the upper abdomen and especially in the pancreas. Imaging of the abdomen with somatostatin analogs such as (68)Ga-DOTA-Phe(1)-Tyr(3)-octreotide (DOTATOC) is a standard approach for imaging neuroendocrine cancer, but is still challenging due to physiological and technical considerations in this area. Therefore, the aim of this study was to further investigate the origin of (68)Ga-DOTATOC findings in the pancreas. Forty-three consecutive patients with neuroendocrine tumours were examined by (68)Ga-DOTATOC positron emission tomography (PET)/CT for staging or restaging. As imaging of the upper abdomen is frequently affected by breathing artefacts, PET and CT data were analysed for misalignment and rearranged if necessary. Any noticeable uptake in the pancreas was described. Tracer uptake in the head of the pancreas and the liver was measured by means of maximum and average standard uptake value (SUV(max), SUV(av)). The reference standards (malignant versus benign) for correlation with PET findings were clinical and radiological follow-up (mean follow-up time 14 months) (n = 37) or histological confirmation (n = 6). In 23 of 43 studies (54%) misalignment between PET and CT data was found with a mean value of 1.4 cm. Visual assessment demonstrated that 20 of 43 scans (46.6%) showed no uptake in the head of the pancreas. Of 43 scans, 23 (53.4%) showed noticeable uptake with focal pattern in the head of the pancreas in 10 scans and irregular pattern in 13 scans. Follow-up indicated malignant pancreatic lesions in three patients. The pancreatic head to liver SUV(av) ratios in these patients ranged from 1.62 to 6.85, whereas in cases of uptake without known malignancy ratios ranged from 0.56 to 1.19. Considering SUV(max), the ratio ranged from 3.24 to 9.1 and from 0.84 to 1.47, respectively. No statistically significant difference was noted between uptake in the head of the pancreas and the liver in patients without malignant pancreatic tumours (p > 0.05). (68)Ga-DOTATOC uptake in the head of the pancreas is a common finding in patients undergoing (68)Ga-DOTATOC PET/CT. However, this finding most likely represents a physiological condition, especially if the uptake in the pancreatic head is similar to the uptake in the liver (uptake ratio head to liver SUV(av) < 1.4). Therefore, quantification is recommended to avoid false-positive diagnosis. Misalignment due to respiratory motion must always be taken into account.
    European Journal of Nuclear Medicine 07/2011; 38(11):2005-13. DOI:10.1007/s00259-011-1875-0 · 4.53 Impact Factor
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    ChemMedChem 07/2011; 6(10):1789-91. DOI:10.1002/cmdc.201100320 · 3.05 Impact Factor
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    ABSTRACT: Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [(18)F] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [(11)C] Pittsburgh Compound B [PiB]- PET) in Alzheimer's disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other. Twenty patients with mild AD underwent baseline (BL) and follow-up (FU) examination with [(18)F] FDG-PET and [(11)C] PiB-PET. Voxel-by-voxel statistical group comparison (SPM5) was performed between patient BL- and FU-PET data as well as between patients and 15 PiB-negative elderly control subjects, who had undergone identical imaging procedures. To obtain objective measures of regional overlap, Dice similarity coefficients (DSC) between the imaging findings were calculated. Compared with elderly control subjects, AD patients showed typical patterns of BL hypometabolism and BL amyloid deposition, with a similarity of 40% (DSC). Amyloid deposition was more extended than hypometabolism at BL and showed only minor changes over time, whereas significant expansion of hypometabolism was observed, almost exclusively within areas already affected by BL amyloid deposition. Thus, increased similarity of FU hypometabolism with BL amyloid deposition was found (DSC: 47%). Longitudinal regional expansion of cerebral hypometabolism, as a measure of neuronal dysfunction in AD, seems to follow the anatomical pattern of amyloid deposition with temporal delay. This indicates that amyloid-based disruption of neuronal integrity might contribute to the regional expansion of neuronal dysfunction.
    Biological psychiatry 06/2011; 71(9):792-7. DOI:10.1016/j.biopsych.2011.04.023 · 8.93 Impact Factor
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    ABSTRACT: Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or (11)C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of (11)C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.
    06/2011; 2011:175352. DOI:10.1155/2011/175352
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    ABSTRACT: L-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI). We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up. There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%. O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.
    International journal of radiation oncology, biology, physics 05/2011; 81(4):1049-58. DOI:10.1016/j.ijrobp.2010.07.002 · 4.59 Impact Factor
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    ABSTRACT: Metabolic imaging of gastric cancer is limited due to the 30% of primary tumors that are not (18)F-fluorodeoxyglucose (FDG) avid. In contrast, the proliferation marker (18)F-fluorothymidine (FLT) has been shown to visualize also non-FDG-avid gastric tumors. In this study we tested whether FLT-positron emission tomography (PET) can improve the predictive potential of molecular imaging for assessing response to neoadjuvant therapy in gastric cancer compared with FDG-PET. 45 patients with gastric cancer underwent FDG- and FLT-PET before and 2 weeks after initiation of chemotherapy. FDG/FLT-PET findings and Ki67 immunohistochemistry were correlated with clinical and histopathological response and survival. 14 patients had non-FDG-avid tumors, whereas all tumors could be visualized by FLT-PET. No significant association of clinical or histopathological response with any of the analyzed metabolic parameters [initial standardized uptake value (SUV), SUV after 2 weeks, change of SUV for FDG/FLT] was found. Univariate Cox regression analysis for Ki67 and metabolic parameters revealed significant prognostic impact for survival only for FLT SUV(mean) day 14 (p=0.048) and Ki67 (p=0.006). Multivariate Cox regression analysis (including clinical response, Lauren type, ypN category, and FLT SUV(mean) day 14) revealed Lauren type and FLT SUV(mean) day 14 as the only significant prognostic factors (p=0.006, p=0.002). FLT uptake 2 weeks after initiation of therapy was shown to be the only imaging parameter with significant prognostic impact. Neither FLT-PET nor FDG-PET were correlated with histopathological or clinical response. However, these data must be interpreted with caution due to the single-center trial study design, relatively short follow-up, poor response rates, and unfavorable prognosis.
    Annals of Surgical Oncology 05/2011; 18(12):3316-23. DOI:10.1245/s10434-011-1743-y · 3.94 Impact Factor
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    ABSTRACT: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy is the standard therapy in aggressive B-cell lymphoma. (18)F-FDG PET has high prognostic implications at treatment completion but is limited as an early predictor. Here, we present the results of a prospective study correlating the initial uptake of the in vivo proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) with the clinical outcome of patients with aggressive non-Hodgkin lymphoma treated with R-CHOP. Sixty-six eligible patients were evaluated prospectively with (18)F-FLT PET before R-CHOP. PET was performed 45 min after injection of 300-370 MBq of (18)F-FLT. Mean and maximum standardized uptake values (SUVs) were calculated on a lesion-by-lesion basis. Response was assessed at the end of therapy. International Prognostic Index (IPI) scores and clinical parameters (Ann Arbor stage, lactate dehydrogenase, performance status, extranodal disease) were determined in all patients. Response was assessed according to revised response criteria after the end of therapy. After treatment, patients were followed in intervals from 4 wk to 6 mo (mean follow-up, 23.1 mo [range, 1-63 mo]), and progression-free and overall survival were determined. All lymphoma lesions identified by a reference method ((18)F-FDG PET/CT or multislice CT of the trunk) showed increased focal tracer uptake (mean (18)F-FLT SUV, 7.3 ± 2.5). Response assessment revealed progressive disease in 4, partial response in 3, and complete response (CR) in the remaining 55 patients. The IPI score was predictive for achieving CR (P = 0.034). Importantly, initial mean SUV was also significantly higher in patients who showed progressive disease and partial response than in patients who achieved CR (P = 0.049). In addition, we found a significant correlation between IPI score and initial (18)F-FLT uptake. Taken together, high (18)F-FLT uptake is a negative predictor of response to R-CHOP treatment in aggressive B-cell non-Hodgkin lymphoma and correlates with the IPI score. Thus, (18)F-FLT PET may represent a useful tool for implementing risk-adapted treatment in these patients.
    Journal of Nuclear Medicine 05/2011; 52(5):690-6. DOI:10.2967/jnumed.110.084566 · 5.56 Impact Factor
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    ABSTRACT: (11)C-Choline-positron emission tomography (PET)/computed tomography (CT) is increasingly used in patients with prostate cancer. Another promising technique for assessment of tumor biology is diffusion-weighted MR imaging (DWI). The aim of the study was to compare the functional parameters standardized uptake value (SUV) in PET and apparent diffusion coefficient (ADC) value in DWI of lymph nodes in prostate cancer patients. Fourteen patients with prostate cancer underwent DWI at 1.5T and (11)C-Choline-PET/CT. ADC values and SUVs of all lymph nodes larger than 5 mm (n = 55) were compared by using linear regression analysis. Performance of DWI and (11)C-Choline PET was assessed by receiver operator characteristic curve analysis using histopathology or clinical follow-up as standard of reference. ADC values and SUV showed a moderate but highly significant inverse correlation (r = -0.5144, p < 0.0001). In lymph nodes with low ADC values, the dispersion of SUV was more pronounced. Moreover, a highly significant difference was observed for mean ADC values and SUV in lymph nodes considered as benign or malignant by follow-up/histopathology (ADC 1.60 ± 0.24 vs. 1.09 ± 0.23 × 10(-3) mm(2)/s; SUV 1.82 ± 0.57 vs. 4.68 ± 03.12; p < 0.0001, respectively). These pilot data propose the ADC value in DWI as a new potential imaging biomarker which might provide additional information on tumor pathophysiology compared to the SUV in (11)C-Choline PET/CT.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 04/2011; 13(2):352-61. DOI:10.1007/s11307-010-0337-6 · 2.47 Impact Factor
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    ABSTRACT: We report a novel series of (11)C-labeled imidazo[2,1-b]benzothiazoles (IBTs) as tracers for imaging of cerebral β-amyloid (Aβ) deposits in patients with Alzheimer's disease (AD) by means of positron emission tomography (PET). From a series of 11 compounds, candidates were identified to have a high binding affinity for Aβ. Selected compounds were prepared as O- or N-[(11)C]methyl derivatives and shown to have a high initial brain uptake in wild-type mice (range 1.9-9.2% I.D./g at 5 min). 2-(p-[(11)C]Methylaminophenyl)-7-methoxyimidazo[2,1-b] benzothiazole ([(11)C]5) was identified as a lead based on the combined favorable properties of high initial brain uptake, rapid clearance from normal brain, and high in vitro affinity for Aβ(1-40) (K(i) = 3.5 nM) and Aβ(1-42) (5.8 nM), which were superior to the Pittsburgh compound B (1a). In an APP/PS1 mouse model of AD (Tg), we demonstrate a specific uptake of [(11)C]5 in Aβ-containing telencephalic brain regions by means of small-animal PET that was confirmed by regional brain biodistribution, ex vivo autoradiography, and immunohistochemistry. Analysis of brain sections of Tg mice receiving a single bolus injection of [(11)C]5 and [(3)H]1a together revealed that the tracers bind to Aβ plaques in the brain of Tg mice in a comparable pattern. Taken together, these data suggest that IBTs represent useful PET imaging agents for high-sensitivity detection of Aβ plaques.
    Journal of Medicinal Chemistry 02/2011; 54(4):949-56. DOI:10.1021/jm101129a · 5.48 Impact Factor

Publication Stats

5k Citations
739.89 Total Impact Points

Institutions

  • 2002–2015
    • Technische Universität München
      • • Section of Radiochemistry and Pharmaceutical Radiochemistry
      • • Nuklearmedizinische Klinik und Poliklinik
      München, Bavaria, Germany
    • Universität Bern
      • Institute of Pathology
      Berna, Bern, Switzerland
  • 2013
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2009–2013
    • ABX Advanced Biochemical Compounds Gmbh
      Radeberg, Saxony, Germany
  • 2002–2012
    • Deutsches Herzzentrum München
      • Department of Cardiovascular Surgery
      München, Bavaria, Germany
  • 2007
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2006
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
    • University of Naples Federico II
      Napoli, Campania, Italy
    • Medizinische Universität Innsbruck
      Innsbruck, Tyrol, Austria