Radiation Dosimetry of (-)-[F-18]-Flubatine - Comparison of animal model data with first-in-man results

Aim:(-)-[F-18]-Flubatine (former NCFHEB) is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the putative radiation risk after intravenous application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were determined in pigs and compared to earlier results in mice and humans [SNM2011 No. 1454, 1459]. Method: Whole body dosimetry of (-)-[F-18]-Flubatine was performed in 5 female piglets (age: 44±3.0d, weight: 13.7±1.7kg). The animals were narcotized using 20 mg/kg Ketamine, 2mg/kg Azaperone; 1.5% Isoflurane in 70% N2O/30% O2 and sequentially PET-imaged up to 5h post i. v. injection of 186.6±7.4MBq (-)-[F-18]-Flubatine on a SIEMENS Biograph16 PET/CT-system with 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction (OSEM, 4 iterations, 8 subsets). All relevant organs were defined by volumes of interest using the structural information from the AC-CT. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time and mass scales were adapted to the respective 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), the kidneys (39.9±6.14µSv/MBq) and the Pancreas (33.8±31.5µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.0±0.8 µSv/MBq), the stomach (1.5±0.3µSv/MBq) and the lungs (1.5±0.2µSv/MBq). The ED to humans following an i. v. injection of (-)-Flubatine according to this data is 13.1±0.9 µSv/MBq. Conclusion: As true for other PET-Tracers too, preclinical incorporation radiation dosimetry underestimates the ED to humans. The ED by (-)-[F-18]-Flubatine yielded from pig- (this study) and mice- (14.2µSv/MBq) studies compared to human dosimetry data (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 in preparation prior to early phase clinical trials. References: The trial is granted by Strahlenschutzseminar in Thüringen e. V.