Towards automated solid phase radiofluorination for dose-on-demand PET: retention of activity by solid support

On-column [¹⁸F]fluoride trapping and radiofluorination of 2-(naphthalen-1-yl)ethyl-4-methylbenzenesulfonate (C₁₀H₇(CH₂)₂OTs), performed on polystyrene supported phosphazene base PS-P^tBu₂ yielded [¹⁸F]1-(2-fluoroethyl)naphthalene ([¹⁸F]C₁₀H₇(CH₂)₂F) in 50% radiochemical yield but left up to 43% of activity unreacted on the resin. This activity could be eluted with Kryptofix/K₂CO₃ and then used for conventional radiofluorination of the same substrate, suggesting that the column-retained activity was present in the form of [¹⁸F]fluoride entrapped in polymer matrix. An approach to minimize the amount of entrapped [¹⁸F]fluoride by use of glass beads functionalized with alkylsilane-derivatized phosphazene residues was attempted but was stymied by fluorolysis/hydrolysis of the alkylsilane spacer. The results suggest that the key to high yield of on-column radiofluorination is to minimize the residual [¹⁸F]fluoride absorption in the matrix by the judicious choice of solid support.