TY  - JOUR
A1  - Eberlein, Uta
A1  - Peper, Michel
A1  - Fernández, Maria
A1  - Lassmann, Michael
A1  - Scherthan, Harry
T1  - Calibration of the \(\gamma\)-H2AX DNA double strand break focus assay for internal radiation exposure of blood lymphocytes
JF  - PLoS ONE
N2  - 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.
KW  - in vivo formation
KW  - chromatin mobility
KW  - phosphorylation
KW  - repair
KW  - 53BP1
KW  - damage
KW  - radioiodine therapy
KW  - thyroid cancer
KW  - histone H2AX
KW  - dose response
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148697
VL  - 10
IS  - 4
ER  - 
TY  - JOUR
A1  - Wester, Hans Jürgen
A1  - Keller, Ulrich
A1  - Schottelius, Margret
A1  - Beer, Ambros
A1  - Philipp-Abbrederis, Kathrin
A1  - Hoffmann, Frauke
A1  - Šimeček, Jakub
A1  - Gerngross, Carlos
A1  - Lassmann, Michael
A1  - Herrmann, Ken
A1  - Pellegata, Natalia
A1  - Rudelius, Martina
A1  - Kessler, Horst
A1  - Schwaiger, Markus
T1  - Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging
JF  - Theranostics
N2  - Chemokine ligand-receptor interactions play a pivotal role in cell attraction and cellular trafficking, both in normal tissue homeostasis and in disease. In cancer, chemokine receptor-4 (CXCR4) expression is an adverse prognostic factor. Early clinical studies suggest that targeting CXCR4 with suitable high-affinity antagonists might be a novel means for therapy. In addition to the preclinical evaluation of [\(^{68}\)Ga]Pentixafor in mice bearing human lymphoma xenografts as an exemplary CXCR4-expressing tumor entity, we report on the first clinical applications of [\(^{68}\)Ga]Pentixafor-Positron Emission Tomography as a powerful method for CXCR4 imaging in cancer patients. [\(^{68}\)Ga]Pentixafor binds with high affinity and selectivity to human CXCR4 and exhibits a favorable dosimetry. [\(^{68}\)Ga]Pentixafor-PET provides images with excellent specificity and contrast. This non-invasive imaging technology for quantitative assessment of CXCR4 expression allows to further elucidate the role of CXCR4/CXCL12 ligand interaction in the pathogenesis and treatment of cancer, cardiovascular diseases and autoimmune and inflammatory disorders.
KW  - acute myeloid leukemia
KW  - prognostic value
KW  - therapeutic target
KW  - chemokine receptor
KW  - CXCR4
KW  - lymphoma
KW  - in vivo imaging
KW  - positron emission tomography
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144537
VL  - 5
IS  - 6
ER  -