Purpose: 6-[F]Fluorodopamine (4-(2-aminoethyl)-5-[F]fluorobenzene-1,2-diol, 6-[F]FDA) is a tracer for imaging sympathetically innervated tissues. Previous electrophilic labelling methods produced 6-[F]FDA with low specific radioactivity (SA) which has limited its wider use. Our aim was to employ electrophilic labelling and increase the SA to around 15 GBq/μmol. We also sought to determine an extensive biodistribution pattern for 6-[F]FDA in rats in order to thoroughly identify tissues with dense sympathetic innervation that were specifically labelled with 6-[F]FDA. In addition, to investigate the safety profile of 6-[F]FDA in larger animals, we performed in vivo studies in pigs. Methods: 6-[F]FDA was synthesised using high SA electrophilic [F]F as the labelling reagent. Biodistribution and metabolism of 6-[F]FDA was determined ex vivo in rats, and in vivo studies were done in pigs. Results: 6-[F]FDA was synthesised with 2.6 ± 1.1% radiochemical yield. The total amount of purified 6-[F]FDA was 663 ± 291 MBq at the end of synthesis (EOS). SA, decay corrected to EOS, was 13.2 ± 2.7 GBq/μmol. Radiochemical purity exceeded 99.0%. Specific uptake of 6-[F]FDA was demonstrated in heart, lung, pancreas, adrenal gland, lower large intestine (LLI), eye, thyroid gland, spleen and stomach tissue. 6-[F]FDA in rat plasma declined rapidly, with a half-life of 2 min, indicating fast metabolism. In vivo PET studies in pigs confirmed the tracer could be used safely without pharmacological effects. Conclusion: 6-[F]FDA was synthesised with good radiopharmaceutical quality and yields high enough for several human PET studies. The SA of 6-[F]FDA was improved by 50- to 500-fold compared to previous electrophilic methods. Uptake of 6-[F]FDA was specific in various peripheral organs, indicating that 6-[F]FDA PET can be used to investigate sympathoneural functions beyond cardiac studies when higher specific uptake is achieved. [ABSTRACT FROM AUTHOR]