Purpose The sphingosine-1-phosphate receptor-1 (S1PR 1 ) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR 1 -specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR 1 radiotracer, [ 18 F]TZ4877, in nonhuman primates. Procedures: [ 18 F]TZ4877 was produced via nucleophilic substitution of tosylate precursor with K[ 18 F]/F - followed by deprotection. Brain PET imaging data were acquired with a Focus220 scanner in two Macaca mulatta (6, 13 years old) for 120-180 min following bolus injection of 118-163 MBq [ 18 F]TZ4877, with arterial blood sampling and metabolite analysis to measure the parent input function and plasma free fraction ( f P ). Each animal was scanned at baseline, 15-18 min after 0.047-0.063 mg/kg of the S1PR 1 inhibitor ponesimod, 33 min after 0.4-0.8 mg/kg of the S1PR 1 -specific compound TZ82112, and 167-195 min after 1 ng/kg of the immune stimulus endotoxin. Kinetic analysis with metabolite-corrected input function was performed to estimate the free fraction corrected total distribution volume ( V T / f P ). Whole-body dosimetry scans were acquired in 2 animals (1M, 1F) with a Biograph Vision PET/CT System, and absorbed radiation dose estimates were calculated with OLINDA. Results [ 18 F]TZ4877 exhibited fast kinetics that were described by the reversible 2-tissue compartment model. Baseline [ 18 F]TZ4877 f P was low (< 1%), and [ 18 F]TZ4877 V T / f P values were 233-866 mL/cm 3 . TZ82112 dose-dependently reduced [ 18 F]TZ4877 V T / f P , while ponesimod and endotoxin exhibited negligible effects on V T / f P , possibly due to scan timing relative to dosing. Dosimetry studies identified the critical organs of gallbladder (0.42 (M) and 0.31 (F) mSv/MBq) for anesthetized nonhuman primate. Conclusions [ 18 F]TZ4877 exhibits reversible kinetic properties, but the low f P value limits quantification with this radiotracer. S1PR 1 is a compelling PET imaging target, and these data support pursuing alternative F-18 labeled radiotracers for potential future human studies.