ABSTRACT
The most common reaction used in the preparation of 18F-labelled radiotracers starts with a nucleophilic substitution reaction using a precursor bearing a good leaving group. Since the nucleophilic properties of the 18F-anion are compromised in the presence of water, a pre-purification step is required. This step consists of retaining 18F-in an anion-exchange column and further eluting with a solution of K2CO3 in water using a cryptand as a phase transfer catalyst (dissolved in acetonitrile), followed by azeotropic evaporation to yield water-free 18F-.Historically, [18F]F2 was produced by irradiation of a mixture of Ne/F2 gas (0.5-1%) with deuterons (5-10 MeV). Although the exact mechanism of [18F]F2 production remains unproven, it is commonly accepted that the 20Ne(d,a)18F nuclear reaction takes place, followed by an isotopic exchange reaction with “carrier” F2to produce [18F]F2. When using this process, two important facts must be taken into consideration: first, the presence of “carrier” F2 in the target yields [18F]F2 with low specific radioactivity, and second, [18F]F2 is easily absorbed by the walls of the target chamber. Hence, pre-conditioning of the target and transfer lines is required to optimise production yields.Production yields of [18F]F2 by deuteron irradiation are low (typically in the order of 9.25 GBq after 1 h of irradiation using 9 MeV deuterons on an irradiated volume of 40 cm3). Hence, an alternative methodology for the production of [18F]F2, which utilised the 18O(p,n)18F nuclear reaction, was developed [2]. This strategy, known as the “double shot method”, consists of two irradiation steps. In the first step, pure [18O]O2 is irradiated with protons and, during irradiation, 18F is generated and absorbed by the walls of the target chamber. After this “first shot”, the oxygen is removed (and recovered/recycled for economy), the target refilled with a mixture of Ne/F2, and a second proton irradiation is carried out. No nuclear reactions of interest take place during the second beam; however, the presence of F2 and 18F (the latter absorbed by the walls of the target chamber) and the high pressures and temperatures facilitate an isotopic exchange reaction with formation of the desired [18F]F2 species, which is transferred to a shielded hot cell for further processing. This method has two main advantages over the traditional method. First, yields are significantly higher (around 45 GBq are produced after 1 h of irradiation using 18 MeV protons on an irradiated volume of
35 cm3), and second, a proton source is used. This is convenient because other commonly used positron emitters, such as 11C and 13N, are also produced by proton irradiation. A schematic representation of the target configuration for the production of [18F]F2 is shown in Fig. 9.2.
