Human biodistribution and dosimetry of [¹⁸F]nifene, an α4β2* nicotinic acetylcholine receptor PET tracer

Introduction: The α4β2* nicotinic acetylcholine receptor (nAChR) system is implicated in many neuropsychiatric pathologies. [¹⁸F]Nifene is a positron emission tomography (PET) ligand that has shown promise for in vivo imaging of the α4β2* nAChR system in preclinical models and humans. This work establishes the radiation burden associated with [¹⁸F]nifene PET scans in humans.

Methods: Four human subjects (2M, 2F) underwent whole-body PET/CT scans to determine the human biodistribution of [¹⁸F]nifene. Source organs were identified and time-activity-curves (TACs) were extracted from the PET time-series. Dose estimates were calculated for each subject using OLINDA/EXM v1.1.

Results: [¹⁸F]Nifene was well tolerated by all subjects with no adverse events reported. The mean whole-body effective dose was 28.4±3.8 mSv/MBq without bladder voiding, and 22.6±1.9 mSv/MBq with hourly micturition. The urinary bladder radiation dose limited the maximum injected dose for a single scan to 278 MBq without urinary bladder voiding, and 519 MBq with hourly voiding.

Conclusions: [¹⁸F]Nifene is a safe PET radioligand for imaging the α4β2* nAChR system in humans.

Advances in knowledge and implications for patient care: This works presents human internal dosimetry for [¹⁸F]nifene in humans for the first time. These results facilitate safe development of future [¹⁸F]nifene studies to image the α4β2* nAChR system in humans.