Introduction

The radiohalogens are particularly attractive to consider as radiolabels for positron emission tomography (PET) radiophamaceuticals. While positron-emitting chlorine has not been utilized, there are several ra-dioiodines and radiobromines and one radiofluorine of great importance to PET (Table 9.1). The chemistry of radioiodine and radiobromine are similar in many respects, but the chemistry of radiofluorine (i.e., fluorine-18) is sufficiently unique to warrant considerable discussion [1]. The emphasis in this chapter is upon fluorine-18 chemistry and 18F-labeled radiopharmaceuticals. This is because 18F, in the form of 2-deoxy-2-[18F]fluoro-D-glucose (FDG), has become the most utilized PET radionuclide. Several positron-emitting radiobromines and radioiodines are not included in Table 9.1, as there is little literature regarding their routine production and use in PET imaging. While 75Br [2, 3] and 122I [4, 5] are included in Table 9.1, they are not discussed further in this chapter. The half-life of 75Br is close to that of 18F, and its production and purification are more complicated. The short half-life of 122I can be an advantage for blood-flow studies, but production constraints have required the use of a high-energy cyclotron and this has limited its application as well.

In general, radioiodines, radiobromines, and fluorine-18 can react as electrophiles or nucleophiles involving species that behave formally as positively charged (X+) or negatively charged (X ) ions, respectively (Figs. 9.1 and 9.2). As the names imply, electrophiles are electron-deficient species that seek electron-rich reactants such as carbon atoms with high local electron densities, and nucleophiles are electron-rich species that seek electron-deficient reactants [6]. While free-radical radiohalogen labeling reactions have been utilized, they tend to be disfavored for PET radiolabeling applications as a result of the difficulty in controlling the regioselectivity of this type of reaction. In contrast, electrophilic and nucleophilic radioiodina-

Table 9.1. Cyclotron-produced PET radiohalogens

Radionuclide

Half-life

Decay Modes (%)

Max. ß+ Energy (MeV)

Production Reactions

18F

109.8 min

ß+ (97) EC (3)

0.635

18O(p,n)18F

20Ne(d,a)18F

76Br

16.1 h

ß+ (57) EC (43)

3.98

75As(3He,2n)76Br

76Se(p,n)76Br

75Br

98 min

ß+ (76) EC (24)

1.74

75As(3He,3n)75Br

78Kr(p,a)75Br

1241

4.2 d

ß+ (25) EC (75)

2.13

124Te(p,n)124I

124Te(d,2n)124I

122I

3.6 min

ß+ (77) EC (23)

3.12

127I(p,6n)122Xe/122I

* Chapter reproduced from Valk PE, Bailey DL, Townsend DW, Maisey MN. Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag London Ltd 2003, 217-236.

Figure 9.1. Nucleophilic reactions relevant to [18F]fluoride.

tions and radiobrominations are more readily controlled and can be regiospecific in many cases. While nucleophilic reactions involving [18F]fluoride can be regiospecific as well, electrophilic [18F]fluorine is very reactive, and its reactions are more difficult to control. Electrophilic fluorinations require special methods, ra-diolabeling precursors, and "taming" reagents that are described in this chapter.

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