New 18F PET Tracers and Novel Methods for their Production

Metastatic estrogen receptor-positive (ER+) breast cancer causes the death of more women than any other type of breast cancer annually. Positron emission tomography (PET) is used to stage cancer metastasis, assess treatment strategies, and monitor the effects of therapy with appropriate radiotracers. 18F-fluoroestradiol (18F-FES) has been used for PET imaging to detect ER+ breast cancer. However, imaging of ER+ tumors with 18F-FES is associated with diverse challenges such as off-target uptake, extensive metabolism, and imaging of soft tissue tumors. Developing the new 18F-tracers for ER+ breast cancer imaging is an underlying need. A novel 18F PET tracer can detect, occurrence and recurrence of ER+ breast cancer with a high-resolution image that will define treatment strategies for breast cancer patients. My dissertation (chapter 1) discusses the strategy, methods, and challenges of late-stage radiofluorination[18F] for the development of new 18F PET tracers. Reductive elimination from diaryliodonium salt is one of the used methods for [18F]-labeling of drug and bioactive molecules. The iodine-mediated [18F]-labeling method has promises and challenges. An ideal novel, efficient and robust radiofluorination method would allow synthesizing a wide range of 18F-labeled drug molecules. In this work, we develop aryl fluorination and radiofluorination methods by regioselective reductive elimination from tetraarylbismuth(V) compounds. As a part of the radiofluorination method development, tri- and/or tetraarylbismuth(V) radiofluorination precursors were synthesized, and selective fluorination of the aryl ligands by a nucleophilic 19F-fluoride source was studied. Chapters 2 & 3 discuss the progress of developing a novel method for 18F-labeling of drugs and bioactive molecules by reductive elimination from bismuth(V) compounds.