Preliminary First-in-Human Pharmacokinetic Evaluation, Dosimetry and Safety of 7-[ ¹⁸ F]-Fluorotryptophan as PET Imaging Agent to Visualize Serotonin Synthesis in the Brain

Abstract Tryptophan (Trp) is the precursor for serotonin synthesis and other biologically relevant metabolites. We evaluated the novel radiotracer 7-[ 18 F]Fluorotryptophan (7-[ 18 F]FTrp) to assess its biodistribution, dosimetry, and potential for imaging brain Trp metabolism in humans. Six healthy volunteers underwent whole-body PET/CT imaging over 5.5 hours following intravenous injection of 7-[ 18 F]FTrp. An additional four subjects underwent dynamic brain PET imaging for 2 hours. Time-activity curves (TACs) were extracted for source organs using VOIs defined on co-registered CT and PET images, and dosimetry was calculated using OLINDA software. The radiotracer showed rapid uptake and distribution, with highest activity observed in the liver, pancreas, salivary glands, in combination with urinary excretion. Brain pharmacokinetic analyses with image-derived input function (IDIF) determined that Patlak analyses were the best fit for brain image analyses. Brain uptake was modest, with highest region-specific accumulation in the pineal gland, which is a known site for serotonin synthesis. The estimated effective dose was within the expected range for 18 F-labeled compounds (14.1 ± 0.2 μSv/MBq). Our findings indicate that 7-[ 18 F]FTrp is safe for human use, demonstrates favorable kinetics for studying both brain and peripheral Trp metabolism, and warrants further exploration in patients with serotonin metabolism disorders.