Application of 106-65-0, Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. 106-65-0, Name is Dimethyl succinate, SMILES is O=C(OC)CCC(OC)=O, belongs to esters-buliding-blocks compound. In a article, author is Syvanen, Stina, introduce new discover of the category.
Fluorine-18-Labeled Antibody Ligands for PET Imaging of Amyloid-beta in Brain
Antibodies are attractive as radioligands due to their outstanding specificity and high affinity, but their inability to cross the blood-brain barrier (BBB) limits their use for CNS targets. To enhance brain distribution, amyloid-beta (A beta) antibodies were fused to a transferrin receptor (TfR) antibody fragment, enabling receptor mediated transport across the BBB. The aim of this study was to label these bispecific antibodies with fluorine-18 and use them for A beta PET imaging. Bispecific antibody ligands RmAb158-scFv8D3 and Tribody A2, both targeting A beta and Tilt, were functionalized with transcyclooctene (TCO) groups and conjugated with 18 F-labeled tetrazines through an inverse electron demand Diels-Alder reaction performed at ambient temperature. F-18-labeling did not affect antibody binding in vitro, and initial brain uptake was high. Conjugates with the first tetrazine variant ([F-18]T1) displayed high uptake in bone, indicating extensive defluorination, a problem that was resolved with the second and third tetrazine variants ([F-18]T2 and [F-18]T3). Although the antibody ligands’ half-life in blood was too long to optimally match the physical half-life of fluorine-18 (t(1/2), = 110 min), [F-18]T3-Tribody A2 PET seemed to discriminate transgenic mice (tg-ArcSwe) with A beta deposits from wild-type mice 12 h after injection. This study demonstrates that F-18-labeling of bispecific, brain penetrating antibodies is feasible and, with further optimization, could be used for CNS PET imaging.
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