The synthesis and development of F-18 labeling substrates for in vivo PET imaging studies
Date
2016
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Publisher
University of Delaware
Abstract
The rapid bioorthogonal reaction between tetrazines and trans-cyclooctenes has been used for a number of scientific applications, one of which includes the rapid assembly of F-18 probes for PET imaging. Due to the fast reactivity between these substrates and efficiency at low concentrations, the tetrazine ligation makes it an unusually well-suited reaction for radiolabeling applications. ☐ Discussed in Chapter 1 is the development of a second generation 18F-labeling system based on a conformationally strained trans-cyclooctene (sTCO). This dienophile, which is two orders of magnitude more reactive than conventional TCO derivatives, was introduced in order to incorporate more stable tetrazines and improve the pharmokinetic properties in comparison to former modified RGD-conjugates developed. Due to the improved tumor uptake and increased blood circulation of this probe, it was of interest to apply these F-18 labeling substrates to larger proteins and other biomolecules. ☐ Chapter 2 focuses on the development of an assay to quantify antibody degree-of-labeling by in-gel fluorescence. For this project, the aim was to add varying stoichiometric amounts of tetrazine in order to modify antibody with about two tetrazines. Achieving a degree of labeling of about two would allow a suitable amount of tetrazine present for 18F-sTCO conjugation for radiolabeling imaging applications while also avoiding over modification of antibody and causing possible defunctionalization. Lastly, Chapter 3 focuses on the preparation of silver nitrate complexes of F-18 labeling precursors to enhance long-term storage and stability of these reagents.