Purpose Many neurological conditions result in the overexpression of the translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are a particularly attractive class of TSPO-specific ligands, prompting the development of several positron emission tomography (PET) radiotracers. This includes F-DPA, a recently reported fluorinated ligand (Ki = 1.7 nM), wherein the fluorine atom is directly linked to the phenyl moiety without the presence of an alkyl or alkoxy spacer chain. Reported here is the preparation of [¹⁸F]F-DPA using [¹⁸F]Selectfluor bis(triflate) and the preliminary evaluation of [¹⁸F]F-DPA in healthy rats. Its metabolic profile and biodistribution in rats are compared with that of [¹⁸F]DPA-714, a closely related structure. Procedures [¹⁸F]F-DPA was synthesized by electrophilic fluorination using [¹⁸F]Selectfluor bis(triflate), [¹⁸F]DPA-714 was synthesized by conventional nucleophilic fluorination. The biodistribution of both radiotracers was compared in Sprague Dawley rats. Radiometabolites of both radiotracers in plasma and brain homogenates were analyzed by radioTLC. Results The radiochemical yield of [¹⁸F]F-DPA was 15 ± 3 % and the specific activity was 7.8 ± 0.4 GBq/μmol. The radiochemical purity exceeded 99 %. The in vivo time activity curves of [¹⁸F]F-DPA demonstrate rapid entry into the brain and a concentration equilibrium at 20–30 min after injection. The metabolic profiles at 90 min after radiotracer injection in the plasma show that unchanged [¹⁸F]F-DPA and [¹⁸F]DPA-714 account for 28.3 ± 6.4 and 11.1 ± 2.6 % of the remaining radioactivity, respectively. In the brain, unchanged [¹⁸F]F-DPA accounts for 93.5 ± 2.8 % of the radioactivity; whereas for [¹⁸F]DPA-714, this value is 53.6 ± 1.6 %. Conclusions [¹⁸F]Selectfluor bis(triflate) was successfully used to label F-DPA with fluorine-18. The labeling position on the aromatic moiety imparts a higher stability compared to [¹⁸F]DPA-714 with regard to in vivo metabolism. [¹⁸F]F-DPA is a promising new radiotracer and warrants further investigation in animal models of disease. Electronic supplementary material The online version of this article (doi:10.1007/s11307-016-1040-z) contains supplementary material, which is available to authorized users.