Winfried Brenner

Publications of Winfried Brenner

• Contribution of (68)Ga-DOTATOC PET/CT to Target Volume Delineation of Skull Base Meningiomas Treated With Stereotactic Radiation Therapy.

  Authors: Reinhold Graf, Fonyuy Nyuyki, Ingo G Steffen, Roger Michel, Daniel Fahdt, Peter Wust, Winfried Brenner, Volker Budach, Reinhard Wurm, Michail Plotkin

  International journal of radiation oncology, biology, physics. 05/2012;

  PURPOSE: To investigate the potential impact of (68)Ga-DOTATOC positron emission tomography ((68)Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) forPURPOSE: To investigate the potential impact of (68)Ga-DOTATOC positron emission tomography ((68)Ga-DOTATOC-PET) in addition to magnetic resonance imaging (MRI) and computed tomography (CT) for retrospectively assessing the gross tumor volume (GTV) delineation of meningiomas of the skull base in patients treated with fractionated stereotactic radiation therapy (FSRT). METHODS AND MATERIALS: The study population consisted of 48 patients with 54 skull base meningiomas, previously treated with FSRT. After scans were coregistered, the GTVs were first delineated with MRI and CT data (GTV(MRI/CT)) and then by PET (GTV(PET)) data. The overlapping regions of both datasets resulted in the GTV(common), which was enlarged to the GTV(final) by adding volumes defined by only one of the complementary modalities (GTV(MRI/CT-added) or GTV(PET-added)). We then evaluated the contribution of conventional imaging modalities (MRI, CT) and (68)Ga-DOTATOC-PET to the GTV(final), which was used for planning purposes. RESULTS: Forty-eight of the 54 skull base lesions in 45 patients showed increased (68)Ga-DOTATOC uptake and were further analyzed. The mean GTV(MRI/CT) and GTV(PET) were approximately 21 cm(3) and 25 cm(3), with a common volume of approximately 15 cm(3). PET contributed a mean additional GTV of approximately 1.5 cm(3) to the common volume (16% ± 34% of the GTV(common)). Approximately 4.5 cm(3) of the GTV(MRI/CT) was excluded from the contribution to the common volume. The resulting mean GTV(final) was significantly smaller than both the GTV(MRI/CT) and the GTV(PET). Compared with the initial GTV(MRI/CT), the addition of (68)Ga-DOTATOC-PET resulted in more than 10% modification of the size of the GTV(final) in 32 (67%) meningiomas CONCLUSIONS: (68)Ga-DOTATOC-PET/CT seems to improve the target volume delineation in skull base meningiomas, often leading to a reduction of GTV compared with results from conventional imaging (MRI and CT).

• Reply: Diagnosis of neuroendocrine tumours and the costs for different tracers - the real problem behind the scenes!

  Authors: Nils F Schreiter, Vikas Prasad, Martin H Maurer, Winfried Brenner

  European journal of nuclear medicine and molecular imaging. 01/2012;

• Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series.

  Authors: Reinhold Graf, Michail Plotkin, Ingo G Steffen, Reinhard Wurm, Peter Wust, Winfried Brenner, Volker Budach, Harun Badakhshi

  Head & face medicine. 01/2012; 8(1):1.

  ABSTRACT: Magnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineateABSTRACT: Magnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy. Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and 68Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) or PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other. Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm3, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm3). 68Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.

• Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours.

  Authors: Nils F Schreiter, Winfried Brenner, Munenobu Nogami, Ralph Buchert, Alexander Huppertz, Ulrich-Frank Pape, Vikas Prasad, Bernd Hamm, Martin H Maurer

  European journal of nuclear medicine and molecular imaging. 09/2011; 39(1):72-82.

  Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies,Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced (68)Ga-DOTATOC PET/CT (n = 29) or (111)In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. A (68)Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 euro. On the other hand, an (111)In-DTPA-octreotide examination resulted in 827 euro total costs. Costs for equipment and material had a share of 460 euro/720 euro for (68)Ga-DOTATOC/(111)In-DTPA-octreotide and labour costs of 89 euro/106 euro. With (68)Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 euro for supplementary imaging per patient; 82% of patients with (111)In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 euro per patient. (68)Ga-DOTATOC PET/CT was considerably cheaper than (111)In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using (68)Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.

• Evaluation of the potential of PET-MRI fusion for detection of liver metastases in patients with neuroendocrine tumours.

  Authors: Nils F Schreiter, Munenobu Nogami, Ingo Steffen, Ulrich-Frank Pape, Bernd Hamm, Winfried Brenner, Rainer Röttgen

  European radiology. 09/2011; 22(2):458-67.

  This study was performed to assess the role of retrospective PET-MRI fusion with Ga-68-DOTA(0)-Phe(1)-Tyr(3)-octreotide (Ga-68-DOTATOC) PET and Gd-EOB-DTPA MRI in the detection of hepatic metastasesThis study was performed to assess the role of retrospective PET-MRI fusion with Ga-68-DOTA(0)-Phe(1)-Tyr(3)-octreotide (Ga-68-DOTATOC) PET and Gd-EOB-DTPA MRI in the detection of hepatic metastases from neuroendocrine tumours (NET). Twenty-two consecutive patients with suspected liver metastases from histopathologically proven NET were examined with Gd-EOB-DTPA MRI and multiphase contrast-enhanced Ga-68-DOTATOC PET/CT. PET and MRI images were retrospectively fused using commercially available software. Two physicians experienced in nuclear medicine and radiology analysed the images to assess diagnostic confidence and characterise liver lesions. A total of 181 lesions were detected. PET-MRI showed a sensitivity of 91.2% (significantly superior to PET/CT; P < 0.05) and a specificity of 95.6% (significantly superior to MRI; P < 0.05). PET/CT had a sensitivity of 73.5% and a specificity of 88.2%. MRI had a sensitivity of 87.6% and a specificity of 86.8%. The area under the curve was 0.98 for PET-MRI, 0.96 for MRI, and 0.89 for PET/CT (P < 0.05). Retrospectively fused PET-MRI was superior to multiphase contrast-enhanced Ga-68-DOTATOC PET/CT and Gd-EOB-DTPA MRI in the detection of NET liver metastases. It was more sensitive than PET/CT and more specific than MRI. Fused PET-MRI therefore seems well suited for surgical and interventional treatment planning of NET liver metastases. • Ga-68-DOTATOC PET-Gd-EOB-DTPA MRI fusion can improve imaging of liver metastases of neuroendocrine tumours. • This technique appears more sensitive than PET/CT for staging NET hepatic metastases. • Ga-68-DOTATOC PET-Gd-EOB-DTPA MRI fusion is more specific than MRI alone.

• Pulmonary FDG uptake without a CT counterpart - a pitfall in interpreting PET/CT images.

  Authors: Nils Schreiter, Munenobu Nogami, Ralph Buchert, Vera Froeling, Winfried Brenner, Felix Diekmann

  Acta radiologica (Stockholm, Sweden : 1987). 06/2011; 52(5):513-5.

  Abnormal pulmonary 18F-FDG foci may occur with benign lesions like pneumonia but seldomly without any pathological CT findings. We report the case of a focal pulmonary 18F-FDG uptake without CTAbnormal pulmonary 18F-FDG foci may occur with benign lesions like pneumonia but seldomly without any pathological CT findings. We report the case of a focal pulmonary 18F-FDG uptake without CT correlate in an initial staging examination of a patient with squamous cell carcinoma of the base of the tongue. A follow-up study did not show any suspicious lesion in this area, but pneumonia with 18F-FDG uptake in another region of the lung. 18F-FDG foci without pathological CT are a rare finding and have been associated with emboli. In the literature two main mechanisms underlying focal 18F-FDG uptake in pulmonary embolism are mentioned: an inflammatory reaction of a pre-existing vascular thrombus and an iatrogenic microembolism caused during injection. In our case the 18F-FDG accumulation was assessed as an iatrogenic pulmonary microembolism.

• Glucose uptake in the placenta, fetal brain, heart and liver related to blood flow redistribution during acute hypoxia.

  Authors: Michael Tchirikov, Miriam Tchirikov, Ralph Buchert, Florian Wilke, Winfried Brenner

  The journal of obstetrics and gynaecology research. 04/2011; 37(8):979-85.

  We used positron emission tomography (PET) with radioactive glucose (F-18-Fluor-Deoxglucose [FDG]) to investigate whether acute maternal hypoxemia causes alterations of glucose uptake of fetal organsWe used positron emission tomography (PET) with radioactive glucose (F-18-Fluor-Deoxglucose [FDG]) to investigate whether acute maternal hypoxemia causes alterations of glucose uptake of fetal organs and the placenta. Investigation was performed under normal conditions and acute hypoxemia in 16 fetal sheep between 108 and 130 days of gestation. Maternal sheep were ventilated with 1.0-1.5% isoflurane/O(2) /N(2) O during whole scanning procedure. Acute hypoxia was induced by reducing O(2) in a ventilated gas mixture to achieve maternal arterial O(2) saturation at a constant level of about 75% baseline. Doppler ultrasound blood flow measurements were performed in the ductus venosus (DV), umbilical artery (UA) and vein (UV). Fetal blood samples were taken by cordocentesis of UV. Dynamic positron emission tomography combined with computed tomography (PET-CT) scans of fetuses were acquired over 60 min after intravenous injection of 300 MBq FDG in the mother. Relative FDG uptake in the fetal brain, heart, and liver was determined on summed images from 40-60 min using manually defined volumes of interest (VOI) normalized to mean FDG uptake in placentomes. Placental blood perfusion reduced significantly from 416.5 ± 116.4 mL/min to 253.5 ± 170.5 mL/min (mean ± SD) during hypoxia. Placental blood supply to the liver decreased from 79.5 ± 14% to 41.1% (P = 0.0001), while DV/UV ratio increased. FDG uptake of the placenta was not changed during hypoxia. Relative FDG uptake in the fetal heart was strongly increased under hypoxia (P = 0.019), whereas it did not differ in the fetal brain and liver. Fetal hypoxia is associated with decreased placental perfusion and liver blood supply. However, glucose uptake was not significantly decreased in the placenta and liver.

• SPECT/CT stabilizes the interpretation of somatostatin receptor scintigraphy findings: a retrospective analysis of inter-rater agreement.

  Authors: Ivayla Apostolova, Swantje Riethdorf, Ralph Buchert, Thorsten Derlin, Winfried Brenner, Janos Mester, Susanne Klutmann

  Annals of nuclear medicine. 05/2010; 24(6):477-83.

  Correlating the anatomical information from CT with the functional information from SPECT improves diagnostic accuracy of somatostatin-receptor-scintigraphy (SRS) in patients with neuroendocrineCorrelating the anatomical information from CT with the functional information from SPECT improves diagnostic accuracy of somatostatin-receptor-scintigraphy (SRS) in patients with neuroendocrine tumors (NET). The aim of the present study was to investigate the impact of dual modality SPECT/CT on the inter-rater agreement in SRS. Twenty-five unselected patients with suspected or histologically proven NET in whom whole body planar imaging and low-dose SPECT/CT had been performed after injection of 200 MBq In-111-octreotide were included retrospectively. Images were interpreted independently by 2 nuclear medicine physicians, an experienced one and an inexperienced one. Both readers first re-evaluated the planar whole-body images alone, then added the SPECT images, and finally the CT-images. Lesions with pathologically increased tracer uptake were categorized according to the following 3-point score: equivocal, probably pathologic, and definitely pathologic. Cohen's linear-weighted kappa coefficient kappa was used to quantify inter-rater agreement. A total number of 50 lesions were described in 23 of the 25 patients. The two readers showed only moderate agreement in the interpretation of the planar findings (kappa = 0.593). Agreement improved to substantial by adding SPECT (kappa = 0.736) and to very good by adding SPECT/CT (kappa = 0.860). SPECT/CT resulted in up-staging of 18% of the lesions and down-staging of 12% compared to planar + SPECT (experienced reader). In addition, SPECT/CT tended to reduce the frequency of indefinite scores (equivocal, probably pathologic), from 18% in planar + SPECT to 6% (p = 0.065). Change of lesion localization by SPECT/CT tended to contribute to the change of lesion score (p = 0.055). The present results suggest that low-dose SPECT/CT stabilizes report quality in SRS by improving inter-rater agreement.

• Combined correction of recovery effect and motion blur for SUV quantification of solitary pulmonary nodules in FDG PET/CT.

  Authors: Ivayla Apostolova, Rafael Wiemker, Timo Paulus, Sven Kabus, Thomas Dreilich, Jörg van den Hoff, Michail Plotkin, Janos Mester, Winfried Brenner, Ralph Buchert, Susanne Klutmann

  European radiology. 03/2010; 20(8):1868-77.

  We evaluate a fully data-driven method for the combined recovery and motion blur correction of small solitary pulmonary nodules (SPNs) in F-18 fluorodeoxyglucose (FDG) positron emission tomographyWe evaluate a fully data-driven method for the combined recovery and motion blur correction of small solitary pulmonary nodules (SPNs) in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). The SPN was segmented in the low-dose CT using a variable Hounsfield threshold and morphological constraints. The combined effect of limited spatial resolution and motion blur in the SPN's PET image was then modelled by an effective Gaussian point-spread function (psf). Both isotropic and non-isotropic psfs were used. To validate the method, PET/CT measurements of the NEMA/IEC spheres phantom were performed. The method was applied to 50 unselected SPNs <or=30 mm from routine patient care. Recovery of standardised uptake value (SUV) in the phantom image was significantly improved by combined recovery and motion blur correction compared with recovery-only correction, particularly with the non-isotropic model (residual average error 10%). In the patient images, automated segmentation and fit of the effective psf worked properly in all cases. Volume-equivalent diameter ranged from 4.9 to 27.8 mm. Uncorrected maximum SUV ranged from 0.9 to 13.3. Compared with recovery-only correction, combined correction with the non-isotropic model resulted in a 'relevant' (>or=30%) SUV increase in 47 SPNs (94%). Correction of both recovery and motion blur is mandatory for accurate SUV quantification of SPNs.

• Identification of transport processes in bioirrigated muddy sediments by [18F]fluoride PET (Positron Emission Tomography).

  Authors: Andrea Roskosch, Jörg Lewandowski, Ralf Bergmann, Florian Wilke, Winfried Brenner, Ralph Buchert

  Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine. 02/2010; 68(6):1094-7.

  In aquatic environments transport processes across the sediment-water interface are intensified by bioirrigating macrozoobenthos. Transport processes caused by Chironomus plumosus larvae dwelling inIn aquatic environments transport processes across the sediment-water interface are intensified by bioirrigating macrozoobenthos. Transport processes caused by Chironomus plumosus larvae dwelling in U-tubes were investigated by dynamic small animal Positron Emission Tomography (PET) with [18F]fluoride. Significant tracer transport from the burrows into the sediment was detected; penetration was deeper at the outlet branch of the burrow than at the inlet branch. Hence, advection plays a significant role in exchange between water in the burrows and muddy sediment.

• Impact of additional SPECT in bone scanning in tumor patients with suspected metastatic bone disease.

  Authors: Ivayla Apostolova, Elif Gölcük, Karl Bohuslavizki, Ralph Buchert, Winfried Brenner

  Annals of nuclear medicine. 11/2009;

  OBJECTIVE: The aim of this study was to investigate the additional value of single-photon emission computed tomography (SPECT) for patient staging compared to planar bone scanning in an unselectedOBJECTIVE: The aim of this study was to investigate the additional value of single-photon emission computed tomography (SPECT) for patient staging compared to planar bone scanning in an unselected cohort of cancer patients. METHODS: The study included 271 consecutive tumor patients in whom planar imaging and two-bed position SPECT of the spine and the pelvis had been performed. Retrospective image interpretation was performed independently for planar and SPECT scans. Findings were categorized as 'benign', 'equivocal', or 'malignant' on a lesion base, and as 'no metastatic disease', 'equivocal', or 'metastatic disease' on a patient base. RESULTS: 447 lesions were detected by SPECT. Missing of lesions in planar images was rare (4.3% of all SPECT lesions). Planar findings differed from SPECT findings in 149 lesions (33.3%). Most of these 'inconsistent' lesions were rated as equivocal in the planar images but benign (14.5% of all lesions) or malignant (11.0%) by SPECT. On a patient base, 81.6% of patients with planar equivocal staging were classified as either benign (55.3%) or malignant (26.3%) by SPECT. Patients definitively staged as 'no metastatic disease' or 'metastatic disease' in planar images were staged differently by SPECT in only 3.7% of cases (up-staging in 2.6% and down-staging in 1.1%). CONCLUSIONS: Single-photon emission computed tomography changed a definite staging as based on planar images in less than 4% of the patients. In patients with planar equivocal staging, however, SPECT allowed a definite diagnosis in more than 80% of these cases, and, thus, should be performed routinely in patients with equivocal findings.

• Potential impact of (68)Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas.

  Authors: Fonyuy Nyuyki, Michail Plotkin, Reinhold Graf, Roger Michel, Ingo Steffen, Timm Denecke, Lilli Geworski, Daniel Fahdt, Winfried Brenner, Reinhard Wurm

  European journal of nuclear medicine and molecular imaging. 09/2009;

  PURPOSE: Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planningPURPOSE: Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with (68)Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of (68)Ga-DOTATOC-PET/CT on the definition of the "gross tumour volume" (GTV) in meningiomas, in order to assess the potential value of this method. METHODS: Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and (68)Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. RESULTS: 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV(CT/MRI) was 22(+/-19)cm(3); GTV(PET) was 23(+/-20)cm(3). Additional GTV, obtained as a result of PET was 9(+/-10)cm(3) and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7(+/-11)cm(3)). Common GTV as obtained by both CT/MRI and PET was 15(+/-14)cm(3). The mean bi-directional difference between the GTV(CT/MRI) and GTV(PET) accounted to 16(+/-15)cm(3) (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. CONCLUSION: (68)Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. (68)Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas.

• [18F]Fluorodeoxyglucose Positron Emission Tomography in Nonseminomatous Germ Cell Tumors After Chemotherapy: The German Multicenter Positron Emission Tomography Study Group.

  Authors: Karin Oechsle, Michael Hartmann, Winfried Brenner, Stephan Venz, Lothar Weissbach, Christiane Franzius, Sabine Kliesch, Stephan Mueller, Susanne Krege, Ruediger Heicappell, Roland Bares, Carsten Bokemeyer, Maike de Wit

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 12/2008;

  PURPOSE: In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospectivePURPOSE: In patients with metastatic nonseminomatous germ cell cancer (NSGCT), residual masses after chemotherapy (CTX) can consist of vital carcinoma, mature teratoma, or necrosis. This prospective trial has evaluated the accuracy of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the prediction of histology compared with computed tomography (CT) and serum tumor markers (STM). PATIENTS AND METHODS: A total of 121 patients with stage IIC or III NSGCT scheduled for secondary resection after cisplatin-based CTX were included. FDG-PET was performed after completion of CTX. All results were confirmed by histopathology and correlated to STM and CT. RESULTS: Prediction of tumor viability with FDG-PET was correct in 56%, which did not reach the expected clinically relevant level of 70%, and was not better than the accuracy of CT (55%) or STM (56%). Sensitivity and specificity of FDG-PET were 70% and 48%. The positive predictive values were not significantly different (55%, 61%, and 59% for CT, STM, and PET, respectively). Judging only vital carcinoma as a true malignant finding, the negative predictive value increased to 83% for FDG-PET. CONCLUSION: The presence of vital carcinoma and mature teratoma is common (55%) in residual masses in patients with NSGCT, and CT and STM cannot reliably predict absence of disease. In contrast to prior studies, this prospective trial, which is the only with histologic confirmation in all patients, demonstrated that FDG-PET is unable to give a clear additional clinical benefit to the standard diagnostic procedures, CT and STM, in the prediction of tumor viability in residual masses.

• Pilot Trial on Determinants of Progenitor Cell Recruitment to the Infarcted Human Myocardium.

  Authors: Volker Schächinger, Alexandra Aicher, Natascha Döbert, Rainer Röver, Jürgen Diener, Stephan Fichtlscherer, Birgit Assmus, Florian H Seeger, Christian Menzel, Winfried Brenner, Stefanie Dimmeler, Andreas M Zeiher

  Circulation. 10/2008;

  BACKGROUND: -Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potentialBACKGROUND: -Clinical trials indicate a beneficial effect of intracoronary infusion of progenitor cells on myocardial function in patients with ischemic heart disease. The extent and potential determinants of proangiogenic progenitor cell homing into the damaged myocardium after intracoronary infusion and the underlying mechanisms are still unknown. Method and Results-Circulating proangiogenic progenitor cells isolated from peripheral blood and cultivated for 3 days were labeled with radioactive indium oxine ((111)In-oxine). Radiolabeled proangiogenic progenitor cells (7.6+/-3.0 MBq, mean+/-SD) were administered to patients with previous myocardial infarction and a revascularized infarct vessel at various stages after infarction (5 days to 17 years). Viability of the infarcted myocardium was determined by (18)F-fluorodeoxyglucose-positron emission tomography and microcirculatory function by intracoronary Doppler measurements. One hour after application of progenitor cells, a mean of 6.9+/-4.7% (range, 1% to 19%; n=17) of total radioactivity was detected in the heart, which declined to 2+/-1% after 3 to 4 days. Average activity within the first 24 hours was highest among patients with acute myocardial infarction (</=14 days; 6.3+/-2.9%; n=8) and progressively decreased in patients treated in an intermediate phase (>14 days to 1 year; 4.5+/-3.2%; n=4) or a chronic stage (infarct age >1 year; 2.5+/-1.6%; n=5). Low viability of the infarcted myocardium and reduced coronary flow reserve were significant (P<0.05) predictors of proangiogenic progenitor cell homing. Conclusions-In patients after myocardial infarction undergoing intracoronary infusion of (111)In-oxine-labeled proangiogenic progenitor cells, a substantial amount of radioactivity is detected for several days in the heart, indicating homing of progenitor cells to the myocardium. The amount of proangiogenic progenitor cells retained in the heart decreased progressively with time after the acute myocardial infarction. Proangiogenic progenitor cells preferentially home to extensive acute myocardial infarcts characterized by low viability and reduced coronary flow reserve.

• Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer.

  Authors: Corinna von Forstner, Jan-Hendrik Egberts, Ole Ammerpohl, Dagmara Niedzielska, Ralph Buchert, Pal Mikecz, Udo Schumacher, Kersten Peldschus, Gerhard Adam, Christian Pilarsky, Robert Grutzmann, Holger Kalthoff, Eberhard Henze, Winfried Brenner

  Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 08/2008; 49(8):1362-70.

  Our aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines afterOur aim was to use PET/MRI to evaluate and compare the uptake of 18F-FDG, 3-deoxy-3-18F-fluorothymidine (18F-FLT), and 18F-fluorethylcholine (18F-FEC) in human pancreatic tumor cell lines after xenotransplantation into SCID mice and to correlate tumor uptake with gene expression of membrane transporters and rate-limiting enzymes for tracer uptake and tracer retention. Four weeks after orthotopic inoculation of human pancreatic carcinoma cells (PancTuI, Colo357, and BxPC3) into SCID mice, combined imaging was performed with a small-animal PET scanner and a 3-T MRI scanner using a dedicated mouse coil. Tumor-to-liver uptake ratios (TLRs) of the tracers were compared with gene expression profiles of the tumor cell lines and both normal pancreatic tissue and pancreatic tumor tissue based on gene microarray analysis and quantitative polymerase chain reaction. 18F-FLT showed the highest tumor uptake, with a mean TLR of 2.3, allowing correct visualization of all 12 pancreatic tumors. 18F-FDG detected only 4 of 8 tumors and had low uptake in tumors, with a mean TLR of 1.1 in visible tumors. 18F-FEC did not show any tumor uptake. Gene array analysis revealed that both hexokinase 1 as the rate-limiting enzyme for 18F-FDG trapping and pancreas-specific glucose transporter 2 were significantly downregulated whereas thymidine kinase 1, responsible for 18F-FLT trapping, was significantly upregulated in the tumor cell lines, compared with normal pancreatic duct cells and pancreatic tumor tissue. Relevant genes involved in the uptake of 18F-FEC were predominantly unaffected or downregulated in the tumor cell lines. In comparison to 18F-FDG and 18F-FEC, 18F-FLT was the PET tracer with the highest and most consistent uptake in various human pancreatic tumor cell lines in SCID mice. The imaging results could be explained by gene expression patterns of membrane transporters and enzymes for tracer uptake and retention as measured by gene array analysis and quantitative polymerase chain reaction in the respective cell lines. Thus, standard molecular techniques provided the basis to help explain model-specific tracer uptake patterns in xenotransplanted human tumor cell lines in mice as observed by PET.

• The role of positron emission tomography in the evaluation of residual masses after chemotherapy for advanced stage seminoma.

  Authors: Stefan Hinz, Mark Schrader, Carsten Kempkensteffen, Roland Bares, Winfried Brenner, Susanne Krege, Christiane Franzius, Sabine Kliesch, Ruediger Heicappel, Kurt Miller, Maike de Wit

  The Journal of urology. 04/2008; 179(3):936-40; discussion 940.

  PURPOSE: Treatment in patients with seminoma who have residual or recurrent masses following chemotherapy is still a matter of debate. Surgical resection is currently the most common recommendationPURPOSE: Treatment in patients with seminoma who have residual or recurrent masses following chemotherapy is still a matter of debate. Surgical resection is currently the most common recommendation for masses greater than 3 cm, resulting in overtreatment in up to 70% of those affected. We analyzed the accuracy of preoperative positron emission tomography for predicting viable tumor residuals in patients with seminoma. MATERIALS AND METHODS: In a prospective, multicenter trial computerized tomography and FDG (2-(F-18)-fluoro-2-deoxy-D-glucose) positron emission tomography were performed before surgical resection for residual or recurrent masses in 20 patients who had undergone chemotherapy for stage IIb, IIc or III seminoma. Histopathological findings were directly correlated with positron emission tomography results. RESULTS: Of the patients 18 presented with residual masses and 2 had recurrent masses following chemotherapy. Histopathological assessment revealed viable tumor in 3 patients and benign lesions in 17. All patients with viable tumor were identified correctly by positron emission tomography. No false-negative results were observed but 9 patients had false-positive positron emission tomography results. This resulted in a negative predictive value of 1 (95% CI 0.63-1) and a positive predictive value of 0.25 (95% CI 0.05-0.57) for FDG-positron emission tomography in our patient cohort. CONCLUSIONS: Our data indicate that FDG-positron emission tomography is capable of excluding viable disease in residual masses, even those exceeding 3 cm. Therefore, it may be considered an additional tool to improve patient counseling. However, the decision to perform surgical resection of the residual mass should not be based exclusively on a positive positron emission tomography image since false-positive results appear to be common.

• Reduced thalamic 18F-flurodeoxyglucose retention in adults with neurofibromatosis type 1.

  Authors: Ralph Buchert, Daniel von Borczyskowski, Florian Wilke, Michael Gronowsky, Reinhard E Friedrich, Winfried Brenner, Janos Mester, Malte Clausen, Victor-F Mautner

  Nuclear medicine communications. 02/2008; 29(1):17-26.

  OBJECTIVE: Neurofibromatosis type1 (NF1) is associated with cognitive and motor deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose positron emission tomography (FDG PET) mightOBJECTIVE: Neurofibromatosis type1 (NF1) is associated with cognitive and motor deficits whose pathogenesis is not well understood. 18F-Flurodeoxyglucose positron emission tomography (FDG PET) might be used to investigate putative functional correlates in the brain. METHODS: Whole-body FDG PET including the brain had been performed in 29 NF1 patients suspected for malignant peripheral nerve sheath tumours (20 females, nine males, age 31.2+/-11.8 years). Twenty-nine age-matched and sex-matched subjects without evidence of neurological/psychiatric disease in whom FDG PET had been performed for NF1-unrelated oncological indication served as controls. Individual brain FDG retention images were stereotactically normalized and scaled to a common median retention value within the brain. Scaled FDG retention was compared between the NF1 group and the control group on a voxel-by-voxel base using ANCOVA in SPM2 with the FDG uptake period as covariate. The corrected significance level alpha=0.05 was used. Voxel-based analysis was complemented by volume of interest (VOI)-based analysis using predefined standard VOIs. RESULTS: The voxel-based group comparison revealed a significant reduction of scaled FDG retention in the thalamus of the NF1 subjects within a cluster of 11.6 ml. There were no further significant effects, neither hypo-retention nor hyper-retention. Reduction of relative FDG retention in the thalamus in the NF1 subjects was confirmed by VOI analysis. The magnitude of the reduction was about 8%. CONCLUSIONS: The thalamus appears to be affected in adults with NF1. The observed magnitude of the reduction of scaled thalamic FDG retention in adults is smaller than previously reported in children. This may be consistent with a stabilization of the disease process with age.

• Ecstasy-induced reduction of the availability of the brain serotonin transporter as revealed by [11C](+)McN5652-PET and the multi-linear reference tissue model: loss of transporters or artifact of tracer kinetic modelling?

  Authors: Ralph Buchert, Frank Thiele, Rainer Thomasius, Florian Wilke, Kay Petersen, Winfried Brenner, Janos Mester, Lothar Spies, Malte Clausen

  Journal of psychopharmacology (Oxford, England). 09/2007; 21(6):628-34.

  In a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [(11)C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users ofIn a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [(11)C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users of the drug ecstasy. However, the multi-linear reference tissue method for the quantification of SERT availability used in this study is prone to effects of altered levels of statistical noise that could simulate reduction of SERT. The aim of the present study was to take into account this confound by re-evaluation of the data now using a modelling approach that is rather insensitive to alterations in the level of statistical noise. A total of 116 subjects (30 current, 29 former ecstasy users, 29 drug-naive, 28 polydrug controls) in whom [(11)C](+)McN5652-PET had been performed previously were re-evaluated. The equilibrium specific-to-non-specific partition coefficient V"( 3) was obtained voxel-wise by application of the simplified reference tissue method (SRTM), which provides quite unbiased results up to rather large noise levels. Voxel-based comparisons between the groups were performed using statistical parametric mapping. V"(3) was reduced in the striatum and in the thalamus in current ecstasy users. This was confirmed by volume-of-interest-based analysis. This result suggests that the ecstasy-induced reduction of SERT availability in SERT-rich brain regions reported previously indicates reduced SERT binding potential rather than being an artifact of tracer kinetic modelling. SRTM analysis did not confirm previous findings in neocortical brain areas.

• Occurrence of an artifact in brain 18F-FDG PET with calculated attenuation correction.

  Authors: Daniel von Borczyskowski, Ulrike Schulte, Winfried Brenner, Malte Clausen, Ralph Buchert

  Journal of nuclear medicine technology. 01/2007; 34(4):232-4.

  In infants, brain (18)F-FDG PET often requires sedation. To keep the sedation mild, the PET acquisition time should be kept short. Therefore, calculated attenuation correction is often preferred toIn infants, brain (18)F-FDG PET often requires sedation. To keep the sedation mild, the PET acquisition time should be kept short. Therefore, calculated attenuation correction is often preferred to measured attenuation correction. In addition, the infant should be positioned as comfortably as possible. Here, we report a case in which the infant's fist was near her head, resulting in severe artifacts when calculated attenuation correction was applied. Brain (18)F-FDG PET was performed for localization of a focus in an 11-mo-old girl with West's syndrome. After injection of 120 MBq of (18)F-FDG, a 20-min emission scan was obtained. Then, a 7-min hot transmission scan was acquired with 3 rotating (68)Ge/(68)Ga rod sources. Attenuation was corrected both by calculated attenuation correction and by measured attenuation correction using the transmission scan. Images reconstructed with calculated attenuation correction showed apparently increased (18)F-FDG uptake in the skin of the neck. The fist was not visible on the images because it was outside the reconstructed field of view. The lesion of increased (18)F-FDG uptake was not immediately recognizable as an artifact. It might have been misinterpreted as an active process, such as inflammation, in the skin. However, the lesion showed up neither on images reconstructed with measured attenuation correction nor on images without attenuation correction. Detailed analysis of each step in the calculated attenuation correction revealed that the fist caused the boundary detection algorithm to detect not the boundary of the head but a strongly extended boundary enclosing the fist and large "air areas" between the fist and the head. The result was a significant overestimation and overcorrection of attenuation, particularly in the region of skin near the fist.

• Risk assessment in liposarcoma patients based on FDG PET imaging.

  Authors: Winfried Brenner, Janet F Eary, Willy Hwang, Cheryl Vernon, Ernest U Conrad

  European journal of nuclear medicine and molecular imaging. 11/2006; 33(11):1290-5.

  PURPOSE: Tumor grade and subtype are considered standard parameters for risk assessment in patients with liposarcoma. The aim of this study was to assess the clinical value ofPURPOSE: Tumor grade and subtype are considered standard parameters for risk assessment in patients with liposarcoma. The aim of this study was to assess the clinical value of [(18)F]fluorodeoxyglucose (FDG) PET-derived maximum standardized uptake value (SUV(max)) for prediction of outcome in liposarcoma patients. METHODS: (18)F-FDG PET was performed in 54 patients with liposarcoma prior to therapy. SUV(max) was calculated for each tumor and results were correlated with tumor grade, subtype, and relapse-free survival. RESULTS: SUV(max) ranged from 0.4 to 15.9 (mean 3.6) and was significantly lower in grade I than in grade II and grade III tumors. SUV(max) was 2.3+/-1.7, 3.5+/-1.5, 4.8+/-2.5, and 5.6+/-5.8 in well-differentiated, myxoid/round cell, dedifferentiated, and pleomorphic subtypes, respectively. Borderline differences (p=0.059) were found between tumor SUV(max) in patients with and without relapse. Using a SUV of 3.6 as cut-off, the accuracy in predicting a relapse was 75%. Tumor grade yielded a lower accuracy for predicting relapse (50%), as did tumor subtype (35%). In Kaplan-Meier survival analysis, patients with a SUV(max) >3.6 had a significantly shorter disease-free survival of 21 months compared with 44 months in patients with a SUV(max) </=3.6. Tumor grading and tumor subtype did not yield significant differences. CONCLUSION: Pretherapy tumor SUV obtained by FDG PET imaging was a more useful parameter for risk assessment in liposarcoma than tumor grade or subtype. A SUV(max) of more than 3.6 resulted in a significantly reduced disease-free survival and identified patients at high risk for developing early local recurrences or metastatic disease.