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Objective: After surgical cytoreduction and standard radiochemotherapy of glioblastoma, approved maintenance therapies are lacking. In line with the infiltrative biology of this tumor type, most recurrences are seen around the resection cavity. Adjuvant radio-immunotherapy (RIT) with Lu-177 labeled [for full text, please go to the a.m. URL]

Introduction: Dysregulated activity of matrix metalloproteinases (MMPs) drives a variety of pathophysiological conditions. Non-invasive imaging of MMP activity in vivo promises diagnostic and prognostic value. However, current targeting strategies by small molecules are typically limited with respect to the bioavailability of the labeled MMP binders in vivo. To this end, we here introduce and compare three chemical modifications of a recently developed barbiturate-based radiotracer with respect to bioavailability and potential to image MMP activity in vivo. Methods: Barbiturate-based MMP inhibitors with an identical targeting unit but varying hydrophilicity were synthesized, labeled with technetium-99m, and evaluated in vitro and in vivo. Biodistribution and radiotracer elimination were determined in C57/BL6 mice by serial SPECT imaging. MMP activity was imaged in a MMP-positive subcutaneous xenograft model of human K1 papillary thyroid tumors. In vivo data were validated by scintillation counting, autoradiography, and MMP immunohistochemistry. Results: We prepared three new 99mTc-labeled MMP inhibitors, bearing either a glycine ([99mTc]MEA39), lysine ([99mTc]MEA61), or the ligand HYNIC with the ionic co-ligand TPPTS ([99mTc]MEA223) yielding gradually increasing hydrophilicity. [99mTc]MEA39 and [99mTc]MEA61 were rapidly eliminated via hepatobiliary pathways. In contrast, [99mTc]MEA223 showed delayed in vivo clearance and primary renal elimination. In a thyroid tumor xenograft model, only [99mTc]MEA223 exhibited a high tumor-to-blood ratio that could easily be delineated in SPECT images. Conclusion: Introduction of HYNIC/TPPTS into the barbiturate lead structure ([99mTc]MEA223) results in delayed renal elimination and allows non-invasive MMP imaging with high signal-to-noise ratios in a papillary thyroid tumor xenograft model.

The purpose of this study was to identify previous treatments and biomarker profile features that prognosticate overall survival (OS) in patients with mCRPC receiving 177Lu-PSMA-617. METHODS: 109 mCRPC patients treated with a median of 3 cycles of 177Lu-PSMA-617 were included. Data were analyzed according to OS as well as PSA response patterns with regard to prior therapies, laboratory biomarkers and metastatic extent in univariate as well as multivariate Cox's proportional hazards models. PSA decline was assessed using the lowest PSA levels after the first cycle of therapy (initial PSA response) and during the entire observation period (best PSA response). RESULTS: In total, 54 patients (49.5%) died during the observation period. First and second line chemotherapy were performed in 85% and 26%, and Abiraterone and Enzalutamide were administered in 83% and 85%, respectively. Any initial PSA decline occurred in 55% while 25% showed a PSA decline of ≥50%. The median estimated OS was 9.9 months (95% CI: 7.2-12.5) for all patients. Any initial decline of PSA was associated with significantly prolonged OS (15.5 vs. 5.7 months, p = 0.002). Second line cabazitaxel chemotherapy (6.7 vs. 15.7 months, p = 0.002) and presence of visceral metastases (5.9 vs. 16.4 months, p

Objective: Surgical resection is the therapy of choice in head and neck paraganglioma (HNPGL), however associated with significant morbidity depending on tumor size and localization. In cases of progressive residual or recurrent disease, novel and less aggressive therapeutic options are warranted. Somatostatin[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

BACKGROUNG: Cardiovascular diseases are the leading cause of death worldwide. A prominent cause of cardiovascular events is atherosclerosis, a chronic inflammation of the arterial wall that leads to the formation of so called atherosclerotic plaques. There is a strong clinical need to develop new, non-invasive vascular imaging techniques in order to identify high-risk plaques, which might escape detection using conventional methods based on the assessment of the luminal narrowing. In this context, molecular imaging strategies based on fluorescent tracers and fluorescence reflectance imaging (FRI) seem well suited to assess molecular and cellular activity. However, such an analysis demands a precise and standardized analysis method, which is orientated on reproducible anatomical landmarks, ensuring to compare equivalent regions across different subjects. METHODS: We propose a novel method, Statistical Permutation-based Artery Mapping (SPAM). Our approach is especially useful for the understanding of complex and heterogeneous regional processes during the course of atherosclerosis. Our method involves three steps, which are (I) standardisation with an additional intensity normalization, (II) permutation testing, and (III) cluster-enhancement. Although permutation testing and cluster enhancement are already well-established in functional magnetic resonance imaging, to the best of our knowledge these strategies have so far not been applied in cardiovascular molecular imaging. RESULTS: We tested our method using FRI images of murine aortic vessels in order to find recurring patterns in atherosclerotic plaques across multiple subjects. We demonstrate that our pixel-wise and cluster-enhanced testing approach is feasible and useful to analyse tracer distributions in FRI data sets of aortic vessels. CONCLUSIONS: We expect our method to be a useful tool within the field of molecular imaging of atherosclerotic plaques since cluster-enhanced permutation testing is a powerful approach for finding significant differences of tracer distributions in inflamed atherosclerotic vessels.

PURPOSE: As atherosclerotic plaque ruptures are the primary cause of ischaemic events, their preventive identification by imaging remains a clinical challenge. Matrix metalloproteinases (MMP) are involved in plaque progression and destabilisation and are therefore promising targets to characterize rupture-prone unstable plaques. This study aims at evaluating MMP imaging to discriminate unstable from stable plaque phenotypes. METHODS: ApoE deficient mice (ApoE-/-) on a high cholesterol diet underwent implantation of a tapered cuff around the right common carotid artery (CCA) inducing a highly inflamed atherosclerotic plaque upstream (US) and a more stable plaque phenotype downstream (DS) of the cuff. 8 weeks after surgery, the MMP inhibitor-based photoprobe Cy5.5-AF443 was administered i.v. 3h prior to in situ and ex vivo fluorescence reflectance imaging of the CCAs. Thereafter, CCAs were analysed regarding plaque size, presence of macrophages, and MMP-2 and MMP-9 concentrations by immunohistochemistry and ELISA. RESULTS: We found a significantly higher uptake of Cy5.5-AF443 in US as compared to DS plaques in situ (1.29 vs. 1.06 plaque-to-background ratio; p

Fragestellung: Trotz zahlreicher neuer Therapieoptionen ist die Behandlung des metastasierten Prostatakarzinoms (mPCa) und insbesondere des metastasierten kastrationsresistenten PCa (mCRPC) schwierig und Resistenzbildung auf zugelassene Therapieoptionen sind im Verlauf die Regel. Daher werden dringend[zum vollständigen Text gelangen Sie über die oben angegebene URL], 62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

Fragestellung: Kürzlich entwickelte 68Ga-dotierte Prostata spezifische Membran Antigen (PSMA) Liganden werden zunehmend als Tool zur Rezidiv- oder Metastasendiagnostik beim Prostatakarzinom (PCa) eingesetzt. In dieser Studie untersuchten wir die Nutzbarkeit von PSMA-PET/CTs zur Vorhersage [zum vollständigen Text gelangen Sie über die oben angegebene URL], 62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

One approach to regionally analyze temporal glucose consumption consists in drawing linear profiles over the maximal values measured in the temporal cortical ribbon. The aim of our study was to test the reproducibility of this method and to compare its diagnostic performance to that of visual analysis in patients with complex partial seizures (CPS).Regional cerebral glucose consumption (rCMRGIc) was measured interictally in 25 CPS patients and 10 controls using F-18-deoxyglucose and the positron emission tomography (PET) camera ECAT EXACT 47. The PET scans were visually analyzed for the occurrence of unilateral temporal hypometabolism. Furthermore, rCMRGIc was quantified on six contiguous coronal planes by manually tracing maximal values of temporal glucose consumption, thus creating line profiles of temporal glucose consumption for each side. Indices of asymmetry (ASY) were then calculated from these line profiles in four temporal regions and compared to the corresponding 95% confidence intervals of the control data. All analyses were performed by two observers independently from each other and without knowledge of the clinical findings.The agreement between the two observers with regard to focus lateralization was 96% (kappa = 0.93) on visual analysis and 100% (kappa = 1) on quantitative analysis. There was an excellent agreement with regard to focus lateralization between visual and quantitative evaluation (kappa = 0.8).Quantitation of local temporal rCMRGIc by using linear profile analysis is highly reproducible; for the lateralization of epileptogenic foci, however, this method does not possess significant advantages over the visual evaluation of the scans.

A case of a 24-year-old man is reported: At the age of ten he was injured by a pane of glass in the region of the medial ankle joint. 14 years later a piece of broken glass which was overlooked during wound toilet, had penetrated to the lateral ankle. The foreign body was impacted in the distal fibula which was sensitive to pressure. Our case shows the importance of a careful inspection of every wound. An unrecognized foreign body may cause severe complications later on.

Rheumatoide Arthritis (RA) ist eine progredient verlaufende Autoimmunerkrankung. Charakteristisch für die Erkrankung sind entzündliche Schübe einhergehend mit einer Synovitis, sowie einer chronischen Knorpel-/ Knochendegeneration. Zur Verringerung der krankheitsbedingten Morbidität, sind die Früherkennung und eine genaue Therapieüberwachung elementar. Ziel der Arbeit war die nicht invasive Darstellung der entzündlichen Schlüsselproteine S100A8/9 und MMPs mittels nicht-invasiver Fluoreszenz Reflektanz Bildgebung. Beide Biomarker wurden im RA Tiermodell zu Beginn und während der Resolutionsphase der Entzündung mittels Bildgebung untersucht. Beide Signale waren zu Beginn der Entzündung erhöht und fielen während der Resolutionsphase ab. Veränderungen im klinischen Scoring wurden vor Veränderungen der Biomarker beobachtet. Es wurden erstmals zwei neuartige Tracer basierend auf kleinen Molekülen zur nicht-invasiven, longitudinalen Darstellung wichtiger Entzündungsbiomarker der RA angewendet. Rheumatoid Arthritis (RA) is a progressive and debilitating autoimmune disease characterized by repeated inflammatory flares, synovitis, as well as cartilage and bone destruction. Early recognition and subsequent treatment monitoring of a flare are key to reducing RA morbidity. To this end, we applied Fluorescence Reflectance Imaging (FRI) in a study of the onset and resolution phases of the Collagen Induced Arthritis (CIA) model of RA, monitoring the biomarkers S100A8/9, an initiator of inflammatory response, and Matrix-metalloproteinases (MMPs), enzymes implicated in cartilage and bone destruction as well as tissue remodeling. Signals of both proteins increased and decreased in concert, with an increase in clinical score preceding the biomarkers. For the first time, small molecule tracers targeting S100A8/A9 and MMPs were used simultaneously, longitudinally, to assess inflammatory activity using optical, non-invasive molecular imaging techniques in a model of RA.

Das Auftreten lokoregionärer Lymphknotenmetastasen (LKM) senkt die Überlebenswahrscheinlichkeit von Patienten mit Plattenepithelkarzinomen der Lippe dramatisch. Deshalb ist es notwendig, Hochrisikopatienten für das Vorliegen okkulter Metastasen (cN0) zuverlässig zu identifizieren und das Outcome durch die adäquate Behandlung der Lymphknoten zu verbessern. Risikofaktoren für die Metastasierung und N0 – Management generell werden dabei jedoch kontrovers diskutiert. Leitlinien zur Entscheidungsfindung fehlen bisher und auch die Kombination von Risikofaktoren zur Ableitung eines Prognosemodells wurde in bisherigen Studien nicht durchgeführt. In der vorliegenden Arbeit konnten prä- und intraoperativ leicht erfassbare Risikofaktoren für LKM identifiziert und zu einem Prognosemodell kombiniert werden, das sich gegenüber dem bisherigen Stand der Literatur als vorteilhaft erweist. Hierdurch konnte eine Handlungsempfehlung für die Therapie von Patienten mit initialem N0-Staging formuliert werden.

Aufgrund der Häufigkeit ischämischer Herzkrankheiten befasst sich die Studie mit Korrelationsanalysen zwischen kardiovaskulären Risikofaktoren, bzw. dem HeartScore und Befunden der Myokard-Perfusions-Szintigraphie (MPS). Ziel ist es einen klinischen Algorithmus zu entwickeln, der dazu beiträgt, die Prätestwahrscheinlichkeit für das Vorliegen einer KHK zu erhöhen. Die individuelle Risikoevaluation soll dadurch vereinfacht und präzisiert werden. Der HeartScore ist bei niedrigem Risikoprofil eine geeignete KHK-Screeningmethode. In der „intermediate risk“-Gruppe sollten bei Männern insbesondere die Prädiktoren Myokardinfarkt in der Familie, niedriges HDL und Rauchen und bei Frauen die Prädiktoren Diabetes mellitus, Multimorbidität, hohes Alter und Rauchen berücksichtigt werden, um die Prätestwahrscheinlichkeit für das vorliegen einer KHK zu erhöhen.

Ziel dieser Arbeit war es, eine neue nicht-invasive Methode zur Quantifizierung der Nierenfunktion von Mäusen mittels 18F-Fluorid- PET zu etablieren. Die gewonnen Daten aus der 18F- Fluorid PET zeigen eine gute Korrelation mit der bereits etablierten Methode der TER- MAG3. Die Methode bietet erstmals die Möglichkeit zeitliche Verlaufskontrollen der Nierenfunktion bei Mäusen unter nephrotoxischer Therapie zu erstellen und so den Einfluss verschiedener applizierter Substanzen auf die Funktion der Niere darzustellen. Darüberhinaus ist die seitengetrennte Analyse der Nierenfunktion durch das Verfahren möglich geworden. Großer Vorteil dieser Methode gegenüber anderen Möglichkeiten der quantitativen Nierenfunktionsdiagnostik ist es, dass die Nierenfunktionsbestimmung bei Mäusen durch das PET nicht-invasiv möglich wird und somit die Urin- und Blutprobenkollektion sehr kleiner Volumina nicht mehr notwendig ist. Das hier entwickelte Verfahren reduziert somit verschiedenste, bei invasivem Vorgehen aber nicht zu vermeidende Fehlerquellen und trägt zusätzlich zu einer maßgeblichen Schonung der Versuchstiere bei.