UCLA

This dissertation describes how modern organic chemistry can be used to improve thetoolbox of fluorine-18 (18F) labeled prosthetic groups for thiol radiolabeling. Herein, I report two new prosthetic groups (4-[18F]fluorovinylsulfonyl benzene ([18F]FVSB) and a [18F]fluoroaryl gold(III) complex), their syntheses, scope, and stability.

Chapter One provides a popular science background for those currently outside of thesynthetic chemistry and radiochemistry communities. This is meant to serve as a broad and brief overview of the work detailed in this dissertation while requiring little background knowledge.

Chapter Two provides a brief overview of positron emission tomography (PET) molecularimaging technology and why fluorine-18 is the radioisotope of choice for clinical applications. This chapter details a variety of radiofluorination methods to prepare 18F-labeled arenes as well as a range of 18F-labeled prosthetic groups and their respective reactivities.

Chapter Three discloses the development of [18F]FVSB, an 18F-labeled vinyl sulfone thatis rapidly synthesized via an 18F-deoxyfluorination method. This chapter details the broad scope of [18F]FVSB to radiolabel free thiols in aqueous media while also demonstrating high stability of the 18F-labeled bioconjugates, produced under a variety of conditions.

Chapter Four details the precise operations involved in the manual and fully-automatedradiosynthesis of [18F]FVSB and subsequent peptide labeling, including many minute specifics as well as troubleshooting advice for those who may use this method. Chapter Five demonstrates the design and development of the first gold mediated 18Farylation reagent for thiol-containing substrates. The robust 18F-gold complex is able to rapidly label free thiols in aqueous environments and furnish stable thioaryl bioconjugates.