Molecular targeting of angiogenesis for imaging and therapy

Angiogenesis, i.e. the proliferation of new blood vessels from pre-existing ones, is an underlying process in many human diseases, including cancer, blinding ocular disorders and rheumatoid arthritis. The ability to selectively target and interfere with neovascularisation would potentially be useful in the diagnosis and treatment of angiogenesis-related diseases. This review presents the authors' views on some of the most relevant markers of angiogenesis described to date, as well as on specific ligands which have been characterised in pre-clinical animal models and/or clinical studies. Furthermore, we present an overview on technologies which are likely to have an impact on the way molecular targeting of angiogenesis is performed in the futur

Impact of double reading on NI-RADS diagnostic accuracy in reporting oral squamous cell carcinoma surveillance imaging – a single-center study

Objectives: The Neck Imaging Reporting and Data System (NI-RADS) is an increasingly utilized risk stratification tool for imaging surveillance after treatment for head and neck cancer. This study aims to measure the impact of supervision by subspecialized radiologists on diagnostic accuracy of NI-RADS when initial reading is performed by residents. Methods: 150 CT and MRI datasets were initially read by two trained residents, and then supervised by two subspecialized radiologists. Recurrence rates by NI-RADS category were calculated, and receiver operating characteristic (ROC) curves were plotted. After dichotomization of the NI-RADS system (category 1 vs categories 2 + 3+4 and categories 1 + 2 vs 3 + 4), sensitivity, specificity, positive and negative predictive value were calculated. Results: 26% of the reports were modified by the supervising radiologists. Area under the curve of ROC plots values of the supervision session were higher than those of the initial reading session for both the primary site (0.89 vs 0.86) and the neck (0.94 vs 0.91), but the difference was not statistically significant. For dichotomized NI-RADS category assignments, differences between the initial reading and the supervision session were statistically significant regarding specificity and PPV for the primary site (1 + 2 vs 3 + 4 and 1 vs 2 + 3+4) or even for both sites combined (1 vs 2 + 3+4). Conclusion: NI-RADS enables trained resident radiologists to report surveillance imaging in patients with treated oral squamous cell carcinoma with high discriminatory power. Additional supervision by a subspecialized head and neck radiologist particularly improves specificity of radiological reports

Reliability of NI-RADS criteria in the interpretation of contrast-enhanced magnetic resonance imaging considering the potential role of diffusion-weighted imaging

Objectives: To assess inter- and intrareader agreement of the Neck Imaging Reporting and Data System (NI-RADS) used in contrast-enhanced magnetic resonance imaging (MRI) including analysis of diffusion-weighted imaging (DWI), which is currently not part of the NI-RADS criteria. Methods: This retrospective study included anonymized surveillance contrast-enhanced MRI datasets of 104 patients treated for different head and neck cancers. Three radiologists experienced in head and neck imaging reported findings for the primary site and the neck using NI-RADS criteria in a first step and evaluated DWI sequences for the primary site in a second step. Thirty randomly selected imaging datasets were again presented to the readers. Kappa statistics and observed agreement (A(o)) were calculated. Results: Interreader agreement across all MRI datasets was moderate (kappa(Fleiss) = 0.53) for NI-RADS categories assigned to the primary site, substantial for NI-RADS categories of the neck (kappa(Fleiss) = 0.67), and almost perfect for DWI of the primary site (kappa(Fleiss) = 0.83). Interreader agreement for the primary site was particularly low in cases of cancer recurrence (kappa(Fleiss) = 0.35) and when categories 2a, 2b, and 3 were combined (kappa(Fleiss) = 0.30). Intrareader agreement was considerably lower for NI-RADS categories of the primary site (range A(o) = 53.3-70.0%) than for NI-RADS categories of the neck (range A(o) = 83.3-90.0%) and DWI of the primary site (range A(o) = 93.3-100.0%). Conclusion: Interreader agreement of NI-RADS for reporting contrast-enhanced MRI findings is acceptable for the neck but limited for the primary site. Here, DWI has the potential to serve as a reliable additional criterion

Kompetenzorientierter Übergang vom beruflichen zum hochschulischen Lernen im Kontext wissenschaftlicher Zertifikatsprogramme an der Hochschule Osnabrück

Mit der Öffnung der Hochschulen rücken beruflich vorgebildete Personen aus dem Berufsfeld der Gesundheitsversorgung auch ohne formale Hochschulzugangsberechtigung in den Kreis der Zielgruppen der Hochschulbildung. Diese Personen wählen wissenschaftliche Zertifikatsangebote im Übergang vom beruflichen zum hochschulischen Lernen, um auf dem aktuellsten Stand des Wissens weitergebildet zu werden. Im Rahmen der zeitlich kleineren Bildungseinheiten der Zertifikatsangebote streben sie mit Blick auf zukünftige Herausforderungen im Gesundheitswesen danach, einen wissenschaftlich fundierten Kompetenzaufbau und -ausbau in einem klar definierten Themenfeld zu erhalten, ohne dafür zwangsläufig ein vollständiges Studium absolvieren zu müssen. Die Zielgruppe dieser nicht-traditionell Studierenden ist durch eine starke Heterogenität u.a. hinsichtlich Alter, Berufsbiografie und Familienverpflichtungen geprägt. Die besondere Angebots- und Organisationsstruktur der wissenschaftlichen Zertifikatsangebote ist auf diese Zielgruppe ausgerichtet. Begleitend zu der didaktischen Ausgestaltung des Curriculums sowie der methodischen Vernetzung von Theorie und Praxis ist die Wertschätzung und Validierung bereits beruflich erworbener Kompetenzen ein Anliegen der Zielgruppe. Insofern erweisen sich gezielte Beratungs- und Unterstützungsmaßnahmen, eine zentrierte Förderung der Selbstreflexionsfähigkeit sowie eine individuelle Lern(fortschritts)begleitung zur aktiven Teilnahme an der wissenschaftlichen Weiterbildung als hilfreich. In diesem Beitrag werden Erfahrungen aus pilotierten Zertifikatsangeboten der wissenschaftlichen Weiterbildung und empirische Erkenntnisse aus dem BMBF-geförderten Projekt KeGL vorgelegt

GLUT 5 Is Not Over-Expressed in Breast Cancer Cells and Patient Breast Cancer Tissues

F18 2-Fluoro 2-deoxyglucose (FDG) has been the gold standard in positron emission tomography (PET) oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues

124I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of 131I-L19-SIP radioimmunotherapy

Purpose: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with 131 I-L19-SIP was recently started. In the present study, after GMP production of 124 I and efficient production of 124 I-L19-SIP, we aimed to demonstrate the suitability of 124 I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical 131 I-L19-SIP RIT. Methods: 124 I was produced in a GMP compliant way via 124 Te(p,n) 124 I reaction and using a TERIMO™ module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected 124 I- and 131 I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while 124 I PET images were obtained from mice with tumours of 90%, respectively. Tumour uptake was 7.3±2.1, 10.8±1.5, 7.8±1.4, 5.3±0.6 and 3.1±0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribu- tion results were obtained with 124 I- and 131 I-L19-SIP. Immuno-PET with 124 I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm3 and no adverse uptake in other organs. Conclusions: 124 I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with 124 I-L19-SIP appeared qualified for sensitive imaging of tumour neo- vasculature and for predicting 131 I-L19-SIP biodistribution.ISSN:1619-7070ISSN:1619-708

Transport und Stoffwechsel der Aminosaeure L-Glutamat am Rattenherz

SIGLEAvailable from TIB Hannover: DW 7230 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman