Preclinical Evaluation of a Novel F-Labeled dTCO-Amide Derivative for Bioorthogonal Pretargeted Positron Emission Tomography Imaging.

Pretargeted positron emission tomography (PET) imaging based on the bioorthogonal inverse-electron-demand Diels-Alder reaction between tetrazines (Tz) and -cyclooctenes (TCO) has emerged as a promising tool for solid tumor imaging, allowing the use of short-lived radionuclides in immune-PET applications. With this strategy, it became possible to achieve desirable target-to-background ratios and at the same time to decrease the radiation burden to nontargeted tissues because of the fast clearance of small PET probes. Here, we show the synthesis of novel F-labeled dTCO-amide probes for pretargeted immuno-PET imaging.

Improved stability of a novel fluorine-18 labeled TCO analogue for pretargeted PET imaging.

Introduction: Biorthogonal pretargeted imaging using the inverse electron demand Diels Alder (IEDDA) reaction between tetrazine (Tz) and trans-cyclooctene (TCO) is one of the most attractive strategies in molecular imaging. It allows the use of short-lived radioisotopes such as fluorine-18 for imaging of long circulating vectors with improved imaging contrast and reduced radiation dose. Here we aim to develop a novel F-labeled trans-cyclooctene (TCO) with improved metabolic stability and assess its potential usefulness in a pretargeted PET imaging approach.

Clickable 4-Oxo-β-lactam-Based Selective Probing for Human Neutrophil Elastase Related Proteomes.

Human neutrophil elastase (HNE) is a serine protease associated with several inflammatory processes such as chronic obstructive pulmonary disease (COPD). The precise involvement of HNE in COPD and other inflammatory disease mechanisms has yet to be clarified. Herein we report a copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC, or 'click' chemistry) approach based on the 4-oxo-β-lactam warhead that yielded potent HNE inhibitors containing a triazole moiety.

Development of a novel antibody-tetrazine conjugate for bioorthogonal pretargeting.

Recently, bioorthogonal chemistry based on the Inverse Electron-Demand Diels-Alder (IEDDA) cycloaddition between 1,2,4,5-tetrazines and trans-cyclooctene (TCO) analogues added an interesting dimension to molecular imaging. Until now, antibodies (Abs) were tagged with TCO and after pretargeting they were reacted with tetrazines substituted with reporters. However, TCO tags have the tendency to degrade under physiological conditions, and due to their hydrophobic nature are buried within the protein.