Chemistry of Fluorine- 18 Radiopharmaceuticals

The chemistry of lSF has the reputation of being difficult and this is to a large extent supported by a survey of the literature, where there are many reports of reactions involving 18F where the yields are low and the reactions erratic. However, in the nine years since the last review of the chemistry of ~8F in this journal °) considerable progress has been made in understanding and controlling these difficulties. It would be an exaggeration to claim that all the problems are solved but there are now a number of 18F containing radiopharmaceuticals produced on a daily basis in a reproducible fashion at different centres around the world. The chemistry of lSF can conveniently be divided into electrophilic and nucleophilic reactions with minor contributions from hot atom reactions. There are no clearly demonstrated examples of fluorine radicals being involved in 18F radiopharmacetical chemistry. The reactions can be further divided on the basis of specific activity into carrier added and no carrier added reactions. The specific activity of useful ~SF radiopharmaceuticals is always high, in themCi's per micromole range, but there are occasions when it must be much higher. When the product is toxic or when the biological process being examined is easily saturated, such as with receptor binding ligands and some enzyme inhibitors the specific activity must be in the Ci per micromole range. There has been considerable progress in raising the specific activity of tSF compounds and in understanding the sources of 19F which contaminate laF preparations and cause the compounds to be no carrier added and not carrier free.~2,3) The methods used for producing 18F are reviewed elsewhere in this issue and will not be discussed in any detail here. However, in many cases the reactions used to synthesize a particular product will be dictated by the methods used to make the 18F and in these cases the methods will be briefly discussed.