TY  - JOUR
A1  - Schumann, S.
A1  - Eberlein, U.
A1  - Lapa, C.
A1  - Müller, J.
A1  - Serfling, S.
A1  - Lassmann, M.
A1  - Scherthan, H.
T1  - α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [\(^{223}\)Ra]RaCl\(_{2}\)-treated prostate cancer patients
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
One therapy option for prostate cancer patients with bone metastases is the use of [\(^{223}\)Ra]RaCl\(_{2}\). The α-emitter \(^{223}\)Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [\(^{223}\)Ra]RaCl\(_{2}\).
Methods
Multiple blood samples from nine prostate cancer patients were collected before and after administration of [\(^{223}\)Ra]RaCl\(_{2}\), up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs.
Results
The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h - 4 weeks after administration), the α-track frequency remained elevated.
Conclusion
The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.
KW  - γ-H2AX
KW  - DNA damage
KW  - nuclear medicine
KW  - dosimetry
KW  - α-Emitter
KW  - biokinetics
KW  - prostate cancer
KW  - [\(^{223}\)Ra]RaCl\(_{2}\)
KW  - 53BP1
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265462
SN  - 1619-7089
VL  - 48
IS  - 9
ER  - 
TY  - JOUR
A1  - Müller, J.
A1  - Krenn, V.
A1  - Czub, S.
A1  - Schindler, C.
A1  - Kneitz, C.
A1  - Kerkau, T.
A1  - Stahl-Henning, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Rethwilm, Axel
A1  - ter Meulen, Volker
A1  - Müller-Hermelink, H. K.
T1  - The thymus in SIV infection
N2  - no abstract available
KW  - HIV-Infektion
KW  - Tierversuch
KW  - Tiermodell
KW  - Retroviren-Infektion
KW  - Kongress
KW  - Hamburg
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80265
ER  - 
TY  - JOUR
A1  - Brinkmann, R.
A1  - Schwinn, A.
A1  - Müller, J.
A1  - Stahl-Hennig, C.
A1  - Coulibaly, C.
A1  - Hunsmann, G.
A1  - Czub, S.
A1  - Rethwilm, Axel
A1  - Dörries, R.
A1  - ter Meulen, Volker
T1  - In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus
N2  - The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.
KW  - Virologie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61415
ER  -