Ziel/Aim Recently, we described new Ga-68 labeled neurotensin NTS1R PET ligands [1]. One peptidic PET ligand with high NTS1R affinity (Ki=1.2 nM) was used to explore whether separation of the PET ligand from the precursor of comparable NTS1R affinity (Ki=5.9 nM) affects tracer uptake into the tumor.
Ziel/Aim The neurotensin receptor 1 (NTS1 R) is considered an interesting target for cancer diagnosis and therapy as it is overexpressed in various tumors (e.g. colorectal and pancreatic carcinoma). Applying the concept of functionalized carbamoylated arginines (1), we aimed at the synthesis and in vitro characterization of stable Ga-68 labeled NTS1 R PET ligands derived from neurotensin(8–13) (NT(8–13)).
Abstract Maintaining and modulating the mechanical anisotropy is essential for biological processes. How this is achieved on the microscopic scale in living soft matter is however not always clear. Here we introduce Brillouin Light Scattering Anisotropy Microscopy (BLAM) for mapping the high-frequency viscoelastic anisotropy inside living cells. Following proof-of-principle experiments on muscle myofibers, we apply this to study two fundamental biological processes. In plant cell walls we show how a phase-transition driven switch between anisotropic-isotropic wall properties may lead to asymmetric growth. In mammalian cell nuclei we uncover a spatio-temporally oscillating elastic anisotropy correlated to chromatin condensation, with long range orientational correlations that may provide a dynamic framework for coordinating intra-nuclear processes. Our results highlight the direct and indirect role the high-frequency mechanics can play in providing dynamic structure that lead to the regulation of diverse fundamental processes in biological systems, and offer a means for studying these. BLAM should find diverse biomedical and material characterization applications.
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Ziel/Aim Neurotensin-Rezeptoren werden überexprimiert in Adenokarzinomen von Pankreas, Dickdarm, Lunge, Prostata oder Brustdrüse. Aktuell gibt es neue Markierungsstrategien für NTRL über carbamoyliertes Arginin (1). Die Plasmastabilität dieser neuen Liganden wurde nachgewiesen (2). Wir wollten einen GMP-fähigen Prozess für die Ga-68-Markierung solcher NTRL entwickeln.
Nuclear transfer facilitates the study of the dedifferentiation process of differentiated somatic cells. Cardiomyocytes are a good model of terminally differentiated cells showing a unique gene expression pattern of cardiac marker genes. The purpose of this study was to test bovine cardiomyocytes as donor cells in nuclear transfer. Cardiomyocytes were isolated from fetal heart muscle (3–5 months of gestation), which were obtained at the abbatoir and immediately perfused with cold Custodiol (Dr. Franz Köhler Chemie, Germany) to reduce metabolism and protect the cells against ischaemia. Subsequently, hearts were perfused with collagenase in Krebs-Henseleit buffer (KHB) to dissociate the tissue and isolate single elongated, contractile cells. For nuclear transfer and fusion the cardiomyocytes were rounded up by exposure to increasing calcium concentrations (2.5–200μM) in the culture medium before the cells were incubated in suspension for 46–48 hours in MEM medium plus 10% FCS. Nuclear transfer was performed as described earlier (Lucas-Hahn et al., 2002, Theriogenology 57, 433). As a control, adult female fibroblasts were employed. Fusion rate, cleavage (day 3 of in vitro culture) and development up to the morula/blastocyst (day 7 of in vitro culture) were recorded and statistically analysed with Student’s t-test. A total of 243 nuclear transfer complexes with cardiomyocytes and 127 with fibroblasts were produced. Fusion rates for cardiomyocyte complexes were significantly (P<0.001) lower (28.8%) compared to fibroblasts (84.3%). Cleavage rates were 48.1% for cardiomyocytes and 62.8% for the fibroblast-derived embryos. The developmental capacity to the morula/blastocyst was significantly (P<0.01) reduced for cardiomyocyte (9.4%) compared with the fibroblast-derived (32.4%) reconstructed embryos. Most of the Day 7 embryos were frozen for investigation of gene expression patterns of cardiac marker genes. Staining with Hoechst 33342 for counting total cell numbers revealed that 87.3±20.9 blastocysts were derived from fibroblasts and 100 blastocysts from cardiomyocytes. These results indicate that nuclear transfer with terminally differentiated cardiomyocytes is possible, although with reduced rates. Studies are underway to analyze the gene expression of cardiac marker genes in reconstructed embryos to gain insight into dedifferentiation after nuclear transfer using cardiomyocytes as a model. This study was supported by Deutsche Forschungsgemeinschaft (DFG; Ni 256/16-1)
