Here we report our design and synthesis of 28 new fluorine-containing compounds as potential F-18 radiotracers for CNS imaging of sphingosine-1-phosphate receptor 1 (S1PR1), and determination of their in vitro binding potency and selectivity toward S1PR1 over other S1PR subtypes. Nine potent and selective compounds, 7c&d, 9a&c, 12b, 15b, and 18a-c with IC50 values ranging from 0.6-12.3 nM for S1PR1 and weak binding toward S1PR2, 3, 4, and 5, were further 18F-radiolabeled to produce [18F]7c&d, [18F]9a&c, [18F]12b, [18F]15b, and [18F]18a-c. Multi-step F-18 radiochemistry procedures were investigated for radiosynthesis of [18F]7c&d and [18F]9a&c, and the presumed intermediates were synthesized and authenticated by analytic HPLC. We then performed nonhuman primate (NHP) PET brain imaging studies for eight radiotracers: [18F]7c&d, [18F]9a, [18F]12b, [18F]15b, and [18F]18a-c. Three radiotracers, [18F]7c, [18F]7d, and [18F]15b, had high NHP brain uptake with standardized uptake values (SUVs) at 2 h post-injection of 2.42, 2.84, and 2.00, respectively, and good brain retention. Our ex vivo biodistribution study in rats confirmed [18F]7d had a high brain uptake with no in vivo defluorination. Radiometabolic analysis of [18F]7c and [18F]7d in rat plasma and brain samples found that [18F]7c has a more favorable metabolic profile than [18F]7d. However, the trend of increased brain uptake precludes [18F]7c as a suitable PET radiotracer for imaging S1PR1 in the brain. Further structural optmization is warranted to identify a highly S1PR1-specific radiotracer with rapid brain uptake kinetics.