nuclear track emulsion
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2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rebecca Faresjö ◽  
Gillian Bonvicini ◽  
Xiaotian T. Fang ◽  
Ximena Aguilar ◽  
Dag Sehlin ◽  
...  

Abstract Background Transferrin receptor (TfR1) mediated enhanced brain delivery of antibodies have been studied extensively in preclinical settings. However, the brain pharmacokinetics, i.e. brain entry, distribution and elimination are still not fully understood for this class of antibodies. The overall aim of the study was to compare the brain pharmacokinetics of two BBB-penetrating bispecific antibodies of different size (210 vs 58 kDa). Specifically, we wanted to investigate if the faster systemic clearance of the smaller non-IgG antibody di-scFv3D6-8D3, in comparison with the IgG-based bispecific antibody mAb3D6-scFv8D3, was also reflected in the brain. Methods Wild-type (C57/Bl6) mice were injected with 125I-iodinated ([125I]) mAb3D6-scFv8D3 (n = 46) or [125I]di-scFv3D6-8D3 (n = 32) and euthanized 2, 4, 6, 8, 10, 12, 16, or 24 h post injection. Ex vivo radioactivity in whole blood, peripheral organs and brain was measured by γ-counting. Ex vivo autoradiography and nuclear track emulsion were performed on brain sections to investigate brain and parenchymal distribution. Capillary depletion was carried out at 2, 6, and 24 h after injection of [125I]mAb3D6-scFv8D3 (n = 12) or [125I]di-scFv3D6-8D3 (n = 12), to estimate the relative levels of radiolabelled antibody in brain capillaries versus brain parenchyma. In vitro binding kinetics for [125I]mAb3D6-scFv8D3 or [125I]di-scFv3D6-8D3 to murine TfR were determined by LigandTracer. Results [125I]di-scFv3D6-8D3 showed faster elimination from blood, lower brain Cmax, and Tmax, a larger parenchymal-to-capillary concentration ratio, and a net elimination from brain at an earlier time point after injection compared with the larger [125I]mAb3D6-scFv8D3. However, the elimination rate from brain did not differ between the antibodies. The study also indicated that [125I]di-scFv3D6-8D3 displayed lower avidity than [125I]mAb3D6-scFv8D3 towards TfR1 in vitro and potentially in vivo, at least at the BBB. Conclusion A smaller size and lower TfR1 avidity are likely important for fast parenchymal delivery, while elimination of brain-associated bispecific antibodies may not be dependent on these characteristics.


2020 ◽  
Vol 1555 ◽  
pp. 012005
Author(s):  
D A Artemenkov ◽  
V Bradnova ◽  
E Firu ◽  
M Haiduc ◽  
N K Kornegrutsa ◽  
...  

2018 ◽  
Vol 119 ◽  
pp. 199-203 ◽  
Author(s):  
D.A. Artemenkov ◽  
V. Bradnova ◽  
G.I. Britvich ◽  
E. Firu ◽  
M. Haiduc ◽  
...  

KnE Energy ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 89
Author(s):  
D A Artemenkov ◽  
V Bradnova ◽  
G I Britvich ◽  
E Firu ◽  
M Haiduc ◽  
...  

Study of production of ensembles of alpha-particle triples associated with the Hoyle state (the second excited state 0+ 2 of the 12 C nucleus) in peripheral dissociation of relativistic 12C nuclei is started. Stacks of pellicles of nuclear track emulsion exposed to 12C of energy from hundreds MeV to few GeV per nucleon serve as the material of the study. The Hoyle state decays are reconstructed via measurements of emission angles of α-particles with accuracy that allows one to identify the unstable 8Be nucleus. A role in the Hoyle state of alpha-particle bonds corresponding to 8Be is determined.


2017 ◽  
Vol 48 (6) ◽  
pp. 960-963
Author(s):  
A. A. Zaitsev ◽  
D. A. Artemenkov ◽  
V. Bradnova ◽  
P. I. Zarubin ◽  
I. G. Zarubina ◽  
...  

2017 ◽  
Vol 48 (6) ◽  
pp. 910-913
Author(s):  
K. Z. Mamatkulov ◽  
I. Ambrožová ◽  
D. A. Artemenkov ◽  
V. Bradnova ◽  
E. Firu ◽  
...  

2017 ◽  
Vol 48 (1) ◽  
pp. 147-157 ◽  
Author(s):  
D. A. Artemenkov ◽  
A. A. Zaitsev ◽  
P. I. Zarubin

2017 ◽  
Vol 138 ◽  
pp. 01030
Author(s):  
D. A. Artemenkov ◽  
V. Bradnova ◽  
E. Firu ◽  
M. Haiduc ◽  
R. R. Kattabekov ◽  
...  

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