Design, Synthesis, and Evaluation of a Low-Molecular-Weight (11)C-Labeled Tetrazine for Pretargeted PET Imaging Applying Bioorthogonal in Vivo Click Chemistry.

A low-molecular-weight tetrazine labeled with the short-lived positron emitter carbon-11 was developed as a bioorthogonal PET probe for pretargeted imaging. A method for efficient and fast synthesis of this imaging agent is presented using radiolabeling of a readily available precursor. High reactivity with trans-cyclooctenes was observed and in vivo investigations including PET/MR scanning showed homogeneous biodistribution, good metabolic stability, and rapid excretion in naive mice. These properties are key to the success of bioorthogonal (11)C-PET imaging, which has been shown in a simple pretargeting experiment using TCO-modified mesoporous silica nanoparticles. Overall, this (11)C-labeled tetrazine represents a highly versatile and advantageous chemical tool for bioorthogonal PET imaging and enables pretargeting approaches using carbon-11 for the first time.

Improved and large-scale synthesis of different protected D-glucuronals.

Although different protected D-glucuronals are used as precursors for the preparation of many compounds, standard procedures and large-scale syntheses are still not described in the literature. In the course of the development of different protected d-glucuronyl donors we developed several versatile methods that can be used for fast and reproducible preparation of large amounts of the key intermediates. D-Glucuronolactone was converted to methyl 3,4-di-O-acetyl-D-glucuronal applying a novel one-pot protocol, which allowed for large-scale synthesis. Introduction of silyl and benzyl groups was achieved using optimized procedures. Furthermore 3,4,6-tri-O-acetyl-D-glucal was used as starting material for an improved preparation of benzyl protected D-glucuronal, which significantly accelerates and simplifies similar methods described in the literature.