Fluorine- 18, and compounds labeled

Positron emission tomography (PET) makes use of a short-lived positron emitter such as fluorine-18 to image human tissue with a degree of detail not possible with x-rays. It has been used extensively to study brain function (see illustration) and in medical diagnosis. For example, when the hormone estrogen is labelled with fluorine-18 and injected into a cancer patient, the fluorine-bearing compound is preferentially absorbed by the tumor. The positrons given off by the fluorine atoms are quickly annihilated when they meet... 

The list of compoimds that have been labeled with carbon-11 and fluorine-18 is extensive. Several recent reviews (7-15) have outlined methods of synthesizing compounds labeled with carbon-11 and fluorine-18 and have discussed some of the problems associated with such syntheses. In this chapter we will not attempt to list these syntheses. Instead, by using C-palmitic acid as a specific example, we will... 

Single- or multi-step preparation of [ F]fluoroaryl-type molecular building blocks and some applications A large number of no-carrier-added fluorine-18-labelled aromatic key-intermediates have been synthesised, opening the way to the preparation of more complicated radiopharmaceuticals via multi-step approaches. Scheme 42 non-exhaustively lists a number of para-substituted [ F]fluorobenzene compounds indicating some of their possible chemical interconnections. It also shows some of the precursors for labelling (P1-P7) that have been used for their preparation. 

The Balz-Schiemann and Wallach reactions The Balz-Schiemann reaction (the thermal decomposition of an aryl diazonium salt. Scheme 46) was for many years the only practical method for the introduction of a fluorine atom into an aromatic ring not bearing electron-withdrawing substituents. This reaction, first reported in the late 1800s, was studied in fluorine-18 chemistry as early as 1967 [214]. It involves the generation of an aryl cation by thermal decomposition, which then reacts with solvent, nucleophiles or other species present to produce a substituted aromatic compound. Use of fluorine-18-labelled... 

In fluorine-18 chemistry some enzymatic transformations of compounds already labelled with fluorine-18 have been reported the synthesis of 6-[ F] fluoro-L-DOPA from 4-[ F]catechol by jS-tyrosinase [241], the separation of racemic mixtures of p F]fluoroaromatic amino acids by L-amino acylase [242] and the preparation of the coenzyme uridine diphospho-2-deoxy-2-p F]fluoro-a-o-glucose from [ F]FDG-1-phosphate by UDP-glucose pyrophosphorylase [243]. In living nature compounds exhibiting a carbon-fluorine bond are very rare. 

A. Syntheses and Uses of Organic Compounds Labelled with Fluorine-18... 

Carbon-11 Flumazenil, 6586,87, and the iodine-123 labelled BZP antagonist iomazenil 6688 have found applications with human subjects86-88. Fluorine-18 labelled ligands FEF, 67, and FEI, 68, have been synthesized89 (equation 40) from the corresponding nor compounds 69 and 70 via alkylation with l-fluoro-2-tosyl ethane in 25-30% r.y. and specific activity > 1000 Ci mmol 1 within 90 min (overall reaction time). 

Development of methods for fluorine-18 labeling has been actively pursued in the last two decades (see Figure 1.33) [172, 173]. Nucleophilic and electrophilic fluorinations have been successfully applied to generate an increasingly diverse assortment of chemical structures. Recent application of click chemistry and the use of protic solvents in nucleophilic fluorinations will significantly impact both the types of compounds labeled and the yields obtained. 

A study of the uranium hexafluoride-metal fluoride complexes was undertaken by Sheft et al. (77) by the use of radioactive fluorine-18 exchange methods. The exchangeability of fluorine between uranium hexafluoride and metal fluorides can be used as a measure of the extent to which reaction occurs. If a complex compound actually forms between uranium hexafluoride and a metal fluoride, then the fluorine atoms become equivalent and randomization of the radioactivity occurs. Complete exchange of the fluorine atoms is found to occur between sodium fluoride labeled... 

Whilst the work that we focus on in the first part of this chapter concerns the preparation of tritium- and inevitably deuterium-labeled compounds, examples are given where the benefits can also be applied to the carbon ( C, and C)-labeled area [8]. Also discussed is the use of microwaves in the synthesis of radiopharmaceuticals labeled with positron emitters, such as carbon-11 (ti/2 = 20.4 min) and fluorine-18 (ti/2 = 109.7 min). The short half lives of these radioisotopes, together with the requirements for high radiochemical yield (RCY), radiochemical purity (RCP) and specific activity (SA) can benefit from the advantages that micro-waves provide [8, 9]. 

Compounds labeled with 20-min half-lived carbon-11 were first intro- duced into biomedical research over 40 years ago (1-6). Before the discovery of carbon-14, compounds such as propionic acid (3) and lactic acid (2) labeled with carbon-11 were synthesized and utilized in biochemical research. After the introduction of carbon-14 as a biomedical tracer, interest in the shorter-lived carbon-11 decreased, and only in the past decade has there been renewed interest in labeling compounds with carbon-11 as well as with other short-lived positron-emitters such as oxygen-15, nitrogen-13, and fluorine-18. 

The Elements.—The inorganic chemistry of fluorine has been reviewed for the period 1966—69 by Russian authors/ and Kuhn has produced a concise account of the electrochemistry of this element/ Fluorine-18 tracer reactions have been reviewed by Rowland and co-workers/ with particular emphasis on the labelling of organic compounds. The excitation curve for production by deuteron bombardment of Ne has been measured/ production of up to 20 mCi h has been achieved by the use of a remote-controlled neon target. ... 

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