Activated Platelets in Carotid Artery Thrombosis in Mice Can Be Selectively Targeted with a Radiolabeled Single-Chain Antibody

BACKGROUND: Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. METHODOLOGY/PRINCIPAL FINDINGS: LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111)In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2) vs. 17390 ± 7470 DLU/mm(2); P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111)In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111)In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01). CONCLUSIONS/SIGNIFICANCE: Nuclear imaging with (111)In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis and might be of interest for further developments towards clinical application

Über die Operation der Ariki-Koike-Algebren auf dem Tensorraum

The action of the Ariki-Koike algebra on tensor space is used to show an isomorphism theorem between the Ariki-Koike algebra and a direct sum of matrix rings over tensorproducts of smaller Ariki-Koike algebras. As an application we get Schur-Weyl duality for the action of the Ariki-Koike algebra and the Levi subalgebra of the q-Schur algebra when separation conditions holds.Mit Hilfe der Operation der Ariki-Koike-Algebra auf dem Tensorraum wird ein Isomorphismus zwischen der Ariki-Koike-Algebra und einer direkten Summe von Matrizenringen über Tensorprodukten kleinerer Ariki-Koike-Algebren gezeigt. Als Anwendung ergibt sich, daß die Ariki-Koike-Algebra und die Leviunteralgebra der q-Schur-Algebra Schur-Weyl-Dualität erfüllen, falls die Separationsbedingung erfüllt ist

Library Design

This review aims at giving a short introduction to the most important areas of library design. The description of compounds by descriptors and fingerprints, and similarity-based clustering techniques are illustrated in the context of untargeted library design. For lead finding and lead optimization libraries it touches on ligand-based combinatorial design, structure-based design, docking and scoring techniques, and fragment-based de novo design. It is shown that computational and combinatorial chemistry can be successfully combined in the design process