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Title:I. Facile preparation of ortho-fluorophenols from non-aromatic precursors and investigation of applications to fluorine-18 labeling II. Resin-supported silyl ester precursors for kit-like radiolabeling with fluorine-18
Author(s):Yasui, Norio
Director of Research:Katzenellenbogen, John A.
Doctoral Committee Chair(s):Katzenellenbogen, John A.
Doctoral Committee Member(s):Hergenrother, Paul J.; Lu, Yi; van der Donk, Wilfred A.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):fluorine-18
radiochemistry
fluorination
diazoketone
silyl ester
resin-supported
Abstract:Molecular imaging is a technique that can be used to visualize complex biochemical processes without perturbing living organisms, and it has been playing increasingly important roles for the early detection of disease states and monitoring the results of therapies. Among molecular imaging techniques, Positron Emission Tomography (PET) has significant advantages compared with other techniques, which includes its high sensitivity and high spatial resolution, and most importantly, its ability to provide functional information, whereas MRI or CT provide largely anatomical information. Among commonly used positron-emitting radionuclides, fluorine-18 has a number of preferred characteristics which are, 1) longest half-life, 109 minutes, 2) lowest maximum energy and 3) purest mode of decay. However, F-18 radiolabeling method is still underdeveloped, and thus, practical radiosyntheses are limited to nucleophilic substitution, especially at alkyl positions. Therefore, to extend the utility of F-18 for PET radiotracers, novel radiolabeling methods with F-18 that enable the preparation of a wide variety of radiotracers, rapidly, efficiently and conveniently are in highly demand in the field of radiochemistry. Chapter 1 presents an introduction of PET imaging techniques, and outlines the basics of F-18 radiochemistry, which focuses on the synthetic difficulties associated with the nature of fluoride and especially F-18. It also highlights the current efforts placed on the development of novel fluorination methods toward F-18 radiosynthesis, especially C-F bond formation on electron-rich aromatic rings and use of fluorophilic elements for rapid preparation of radiotracers. Chapter 2 discusses the development of a facile a fluorination method that produces ortho-fluorophenols from non-aromatic precursors. We have found that α-diazocyclohexenones undergo halofluorination with fluoride ion as fluoride source, and the following hydrohalide elimination and tautomerization afford ortho-fluorophenols rapidly. The translation to F-18 radiolabeling was achieved using organic soluble phase transfer catalysis under carrier-added conditions. Although labeling under non-carrier-added conditions is still a work in progress, our current progress points to a new approach to label electron-rich aromatic rings rapidly and at high specific activity (SA). Chapter 3 discusses the development of a kit-like radiosynthetic method using a resin-supported silicon based precursor. We have found that silyl esters have significant advantages over previously reported methods; they undergo F-18 incorporation under very mild conditions, with F-18 water straight from the cyclotron used without any drying. We further developed the resin-supported method which enables simple purification of the radiotracer. The utility of this approach is showcased in three main area of research: prosthetic groups, small molecules and peptides.
Issue Date:2015-07-01
Type:Thesis
URI:http://hdl.handle.net/2142/88254
Rights Information:Copyright 2015 Norio Yasui
Date Available in IDEALS:2015-09-29
Date Deposited:August 201


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