@article{BaurSchedelbeckPulzeretal.2015, author = {Baur, Johannes and Schedelbeck, Ulla and Pulzer, Alina and Bluemel, Christina and Wild, Vanessa and Fassnacht, Martin and Steger, U.}, title = {A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma}, series = {BMC Surgery}, volume = {15}, journal = {BMC Surgery}, number = {93}, doi = {10.1186/s12893-015-0076-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126130}, year = {2015}, abstract = {Background Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin. Case presentation Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred. Conclusion Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.}, language = {en} } @article{ChenWernerJavadietal.2015, author = {Chen, Xinyu and Werner, Rudolf A. and Javadi, Mehrbod S. and Maya, Yoshifumi and Decker, Michael and Lapa, Constantin and Herrmann, Ken and Higuchi, Takahiro}, title = {Radionuclide imaging of neurohormonal system of the heart}, series = {Theranostics}, volume = {5}, journal = {Theranostics}, number = {6}, doi = {10.7150/thno.10900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149205}, pages = {545-558}, year = {2015}, abstract = {Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included.}, language = {en} } @article{DrozdSaenkoBrenneretal.2015, author = {Drozd, Valentina M. and Saenko, Vladimir A. and Brenner, Alina V. and Drozdovitch, Vladimir and Pashkevich, Vasilii I. and Kudelsky, Anatoliy V. and Demidchik, Yuri E. and Branovan, Igor and Shiglik, Nikolay}, title = {Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0137226}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141863}, pages = {e0137226}, year = {2015}, abstract = {One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (I-131) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the I-131-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.}, language = {en} } @article{EberleinPeperFernandezetal.2015, author = {Eberlein, Uta and Peper, Michel and Fern{\´a}ndez, Maria and Lassmann, Michael and Scherthan, Harry}, title = {Calibration of the \(\gamma\)-H2AX DNA double strand break focus assay for internal radiation exposure of blood lymphocytes}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0123174}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148697}, pages = {e0123174}, year = {2015}, abstract = {DNA double strand break (DSB) formation induced by ionizing radiation exposure is indicated by the DSB biomarkers \(\gamma\)-H2AX and 53BP1. Knowledge about DSB foci formation in-vitro after internal irradiation of whole blood samples with radionuclides in solution will help us to gain detailed insights about dose-response relationships in patients after molecular radiotherapy (MRT). Therefore, we studied the induction of radiation-induced co-localizing \(\gamma\)-H2AX and 53BP1 foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per cell values with the in-vitro absorbed doses to the blood for the two most frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers were analyzed. For each experiment several vials containing a mixture of whole blood and radioactive solutions with different concentrations of isotonic NaCl-diluted radionuclides with known activities were prepared. Leukocytes were recovered by density centrifugation after incubation and constant blending for 1 h at 37°C. After ethanol fixation they were subjected to two-color immunofluorescence staining and the average frequencies of the co-localizing \(\gamma\)-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope equipped with a red/green double band pass filter. The exact activity was determined in parallel in each blood sample by calibrated germanium detector measurements. The absorbed dose rates to the blood per nuclear disintegrations occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A linear relationship was found between the number of DSB-marking foci/nucleus and the absorbed dose to the blood for both radionuclides studied. There were only minor nuclide-specific intra-and inter-subject deviations.}, language = {en} } @article{HerrmannQueirozHuellneretal.2015, author = {Herrmann, Ken and Queiroz, Marcelo and Huellner, Martin W. and Barbosa, Felipe de Galiza and Buck, Andreas and Schaefer, Niklaus and Stolzman, Paul and Veit-Haibach, Patrick}, title = {Diagnostic performance of FDG-PET/MRI and WB-DW-MRI in the evaluation of lymphoma: a prospective comparison to standard FDG-PET/CT}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {1002}, doi = {10.1186/s12885-015-2009-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136039}, year = {2015}, abstract = {Background: Use of FDG-PET/CT for staging and restaging of lymphoma patients is widely incorporated into current practice guidelines. Our aim was to prospectively evaluate the diagnostic performance of FDG-PET/MRI and WB-DW-MRI compared with FDG-FDG-PET/CT using a tri-modality PET/CT-MRI system. Methods: From 04/12 to 01/14, a total of 82 FDG-PET/CT examinations including an additional scientific MRI on a tri-modality setup were performed in 61 patients. FDG-PET/CT, FDG-PET/MRI, and WB-DW-MRI were independently analyzed. A lesion with a mean ADC below a threshold of 1.2 x 10\(^{-3}\) mm\(^2\)/s was defined as positive for restricted diffusion. FDG-PET/CT and FDG-PET/MRI were evaluated for the detection of lesions corresponding to lymphoma manifestations according to the German Hodgkin Study Group. Imaging findings were validated by biopsy (n = 21), by follow-up imaging comprising CT, FDG-PET/CT, and/or FDG-PET/MRI (n = 32), or clinically (n = 25) (mean follow-up: 9.1 months). Results: FDG-PET/MRI and FDG-PET/CT accurately detected 188 lesions in 27 patients. Another 54 examinations in 35 patients were negative. WB-DW-MRI detected 524 lesions, of which 125 (66.5 \% of the aforementioned 188 lesions) were true positive. Among the 188 lesions positive for lymphoma, FDG-PET/MRI detected all 170 instances of nodal disease and also all 18 extranodal lymphoma manifestations; by comparison, WB-DW-MRI characterized 115 (67.6 \%) and 10 (55.6 \%) lesions as positive for nodal and extranodal disease, respectively. FDG-PET/MRI was superior to WB-DW-MRI in detecting lymphoma manifestations in patients included for staging (113 vs. 73), for restaging (75 vs. 52), for evaluation of high-(127 vs. 81) and low-grade lymphomas (61 vs. 46), and for definition of Ann Arbor stage (WB-DW-MRI resulted in upstaging in 60 cases, including 45 patients free of disease, and downstaging in 4). Conclusion: Our results indicate that FDG-PET/CT and FDG-PET/MRI probably have a similar performance in the clinical work-up of lymphomas. The performance of WB-DW-MRI was generally inferior to that of both FDG-PET-based methods but the technique might be used in specific scenarios, e.g., in low-grade lymphomas and during surveillance.}, language = {en} } @article{KlaesnerBuchmannGemptetal.2015, author = {Kl{\"a}sner, Benjamin and Buchmann, Niels and Gempt, Jens and Ringel, Florian and Lapa, Constantin and Krause, Bernd Joachim}, title = {Early [\(^{18}\)F]FET-PET in Gliomas after Surgical Resection: Comparison with MRI and Histopathology}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0141153}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139549}, pages = {e0141153}, year = {2015}, abstract = {Background The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [\(^{18}\)F]O-(2-[\(^{18}\)F]-fluoroethyl)-L-tyrosine ([\(^{18}\)F]FET). Methods 25 patients with the suspicion of primary HGG were enrolled. All patients underwent preoperative [\(^{18}\)F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [\(^{18}\)F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up. Results [\(^{18}\)F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48\%) patients and incomplete resection in 6/25 cases (24\%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery. Conclusion Early assessment of the resection status in HGG with [\(^{18}\)F]FET-PET seems to be feasible.}, language = {en} } @article{LapaLinsenmannLueckerathetal.2015, author = {Lapa, Constantin and Linsenmann, Thomas and L{\"u}ckerath, Katharina and Samnick, Samuel and Herrmann, Ken and Stoffer, Carolin and Ernestus, Ralf-Ingo and Buck, Andreas K. and L{\"o}hr, Mario and Monoranu, Camelia-Maria}, title = {Tumor-Associated Macrophages in Glioblastoma Multiforme—A Suitable Target for Somatostatin Receptor-Based Imaging and Therapy?}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0122269}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125498}, pages = {e0122269}, year = {2015}, abstract = {Background Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM) have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A) which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM. Methods 15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68), proliferative activity (Ki67) as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET) imaging using \(^{68}Ga-DOTATATE\) was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry. Results The amount of microglia/macrophages ranged from <10\% to >50\% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns. Conclusion SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.}, language = {en} } @article{LueckerathLapaAlbertetal.2015, author = {L{\"u}ckerath, Katharina and Lapa, Constantin and Albert, Christa and Herrmann, Ken and J{\"o}rg, Gerhard and Samnick, Samuel and Einsele, Herrmann and Knop, Stefan and Buck, Andreas K.}, title = {\(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {10}, doi = {10.18632/oncotarget.3053}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148688}, pages = {8418-8429}, year = {2015}, abstract = {Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79\% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.}, language = {en} } @article{MacedoJavadiHiguchietal.2015, author = {Macedo, Robson and Javadi, Som Mehrbod and Higuchi, Takahiro and Ferreira de Carvalho, Marilia Daniela and Lima Paiva Medeiros, Vanessa de F{\´a}tima and Azevedo, {\´I}talo Medeiros and Lima, Francisco Pignataro and Medeiros, Aldo Cunha}, title = {Heart and systemic effects of statin pretreatment in a rat model of abdominal sepsis. Assessment by Tc\(^{99m}\)-sestamibi biodistribition}, series = {Acta Cir{\´u}rgica Brasileira}, volume = {30}, journal = {Acta Cir{\´u}rgica Brasileira}, number = {6}, doi = {10.1590/S0102-865020150060000003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151887}, pages = {388 -- 393}, year = {2015}, abstract = {PURPOSE: To evaluate the heart and the Tc-99m-sestamibi biodistribution after statin pretreatment in a rat model of abdominal sepsis. METHODS: Twenty-four Wistar rats were randomly distributed into four groups (n=6 per group): 1) sepsis with simvastatin treatment, 2) sepsis with vehicle, 3) sham control with simvastatin and 4) sham control with vehicle. 24 hours after cecal ligation and puncture rats received 1.0MBq of Tc-99m-sestamibi i.v. 30min after, animals were euthanized for ex-vivo tissue counting and myocardium histological analysis. RESULTS: Myocardial histologic alterations were not detected 24 hours post-sepsis. There was significantly increased cardiac Tc-99m-sestamibi activity in the sepsis group with simvastatin treatment (1.9\(\pm\)0.3\%ID/g, p<0.001) in comparison to the sepsis group+vehicle (1.0\(\pm\)0.2\% ID/g), control sham group+ simvastatin (1.2\(\pm\)0.3\% ID/g) and control sham group (1.3\(\pm\)0.2\% ID/g). Significant Tc-99m-sestamibi activity in liver, kidney and lungs was also detected in the sepsis group treated with simvastatinin comparison to the other groups. CONCLUSIONS: Statin treatment altered the biodistribution of Tc-99m-sestamibi with increased cardiac and solid organ activity in rats with abdominal sepsis, while no impact on controls. Increased myocardial tracer activity may be a result of a possible protection effect due to increased tissue perfusion mediated by statins.}, language = {en} } @article{PaschkeLinckeMuelleretal.2015, author = {Paschke, Ralf and Lincke, Thomas and M{\"u}ller, Stefan P. and Kreissl, Michael C. and Dralle, Henning and Fassnacht, Martin}, title = {The Treatment of Well-Differentiated Thyroid Carcinoma}, series = {Deutsches {\"A}rzteblatt International}, volume = {112}, journal = {Deutsches {\"A}rzteblatt International}, doi = {10.3238/arztebl.2015.0452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151636}, pages = {452 -- 458}, year = {2015}, abstract = {Background: Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year. Method: This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years. Results: The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcar cinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90\% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radio active iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90\%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10\%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss. Conclusion: Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.}, language = {en} }