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The success of molecular imaging with positron‐emission tomography (PET) depends on the availability of selective molecular probes labeled with positron‐emitters, such asfluorine‐18 (t1/2 = 109.7 min). No‐carrier‐added (NCA) [18F]fluoride ion (18F–) is the primary reagent for the preparation of 18F‐labeled tracers in high specific activity. In this microreview, we survey current and advancing radiochemical methods and technologies for the use of NCA [18F]fluoride ion in the preparation of 18F‐labeled radiotracers for applications with PET. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A micro-reactor was applied to produce ortho-substituted [ 18 F]fluoroarenes from the reactions of cyclotron-produced [ 18 F]fluoride ion (t 1/2 = 109.7 min) with diaryliodonium salts. The micro-reactor provided a very convenient means for running sequential reactions rapidly with small amounts of reagents under well-controlled conditions, thereby allowing reaction kinetics to be followed and Arrhenius activation energies (E a ) to be measured. Prepared symmetrical iodonium chlorides (Ar 2 I + Cl − ) rapidly (< 8 min) gave moderate (Ar = 2-MeOC 6 H 4 , 51%) to high (Ar = Ph or 2-MeC 6 H 4 , 85%) decay-corrected radiochemical yields (RCYs) of a single radioactive product (Ar 18 F). Reaction velocity with respect to Ar group was 2-MeOC 6 H 4 < Ph < 2-MeC 6 H 4 . Activation energies were in the range 18-28 kcal/mol. Prepared unsymmetrical salts (e.g., 2-RC 6 H 4 I + 2'-R'C 6 H 4 X − ; X = Cl or OTs) also rapidly gave two products (2-RC 6 H 4 18 F and 2-R'C 6 H 4 18 F) in generally high total RCYs (79-93%). Selectivity for product [ 18 F]fluoroarene was controlled by the nature of the ortho substituents. The power of ortho substituents to impart an ortho effect was in the following order, 2,6-di-Me > 2,4,6-tri-Me > Br > Me > Et ∼ i Pr >> H > OMe. For (2-methyphenyl) (phenyl)iodonium chloride, the time-course of reaction product selectivity was constant and consistent with the operation of the Curtin-Hammett Principle. These results will aid in the design of diaryliodonium salt precursors to 18 F-labeled tracers for molecular imaging.

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