Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results

Objectives (-)-[F-18]-Flubatine (former NCFHEB) is a new tracer for neuroimaging of α4β2 nAChRs with PET. To assess the radiation risk, its biodistribution, organ doses (OD) and effective dose (ED) were determined in pigs and compared to earlier results in mice and humans [SNM2011 No. 1454, 1459].

Methods For whole body dosimetry, 5 female piglets (age: 44±3.0d, weight: 13.7±1.7kg) were narcotized (20 mg/kg Ketamine, 2mg/kg Azaperone; 1.5% Isoflurane in 70% N2O/30% O2) and sequentially imaged up to 5h post i.v. injection of 186.6±7.4MBq Flubatine on a PET/CT-system with 7 bed positions (BP) per frame, 1.5-6min/BP, CT-attenuation correction and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time and mass were adapted to the human scale. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103.

Results The highest OD was received by the urinary bladder (49.0±19.4µSv/MBq*) and the kidneys (39.9±6.1*). The highest contribution to the ED was by the urinary bladder (2.0±0.7*) and the stomach (1.5±0.3*). The ED to humans after i.v. injection of (-)-Flubatine is 14.6±3.2*.

Conclusions As true for other PET-Tracers, preclinical dosimetry potentially underestimates the ED to humans. The ED by Flubatine yielded from pig- (this study) and mice- (14.2µSv/MBq) studies compared to human dosimetry (22.6±0.68µSv/MBq) show that animal dosimetry underestimates the potential radiation exposure to humans by 35-37%. This fact needs to be considered in the assessment of the ED to humans prior early phase clinical trials.

Research Support The study was supported by Strahlenschutzseminar in Thüringen e.V