First-In-Human Evaluation of [18F]Fluproxadine for Norepinephrine Transporter PET: Biodistribution, Dosimetry, and...

Current norepinephrine transporter (NET) tracers used for cardiac sympathetic imaging and oncology are limited by radiosynthesis complexity, suboptimal image quality, or operational constraints. [18F]fluproxadine (formerly [18F]AF78) was developed to address these limitations by providing high NET affinity, favorable biodistribution, and an operationally straightforward radiosynthesis. We therefore conducted the first-in-human evaluation of this new class of [18F] labeled NET PET tracer to assess its safety, biodistribution, radiation dosimetry, and imaging characteristics.

In a prospective study, 4 healthy adult volunteers received [18F]fluproxadine (101.8-204.0 MBq). Dynamic whole-body PET/CT acquisitions were obtained 10 times from 1 to 232 minutes postinjection, and vital signs, laboratory tests, and adverse events were monitored. Time-activity curves were generated for major organs, including myocardium from the whole-body scans, and organ-absorbed doses and effective dose were estimated using OLINDA/EXM v2.0 from time-integrated activities. Myocardial uptake and target-to-background behavior were assessed using semiquantitative methods. Radiosynthesis performance and key operational steps were documented to assess practical scalability.

Radiosynthesis of [18F]fluproxadine was operationally straightforward with encouraging yields and fewer specialized steps than some legacy tracers. Imaging was completed without serious adverse events. Biodistribution showed predominant renal clearance; biliary excretion was not observed within the imaging window. Highest organ doses were to the urinary bladder wall and kidneys, with additional uptake in liver, thyroid, salivary glands, and myocardium. The effective dose was 21.6±1.5 µSv/MBq. Myocardial uptake was clearly visualized on whole-body images with favorable target-to-background characteristics at delayed time points, consistent with NET biology and supporting practical cardiac imaging windows.

[18F]fluproxadine demonstrated clear myocardial uptake, acceptable radiation dosimetry comparable to typical 18F PET agents, and an early safety profile without serious adverse events.