First-in-man incorporation dosimetry of (+)-[18F]flubatine

Objectives :

(-)-[¹⁸F]flubatine is successfully used for neuroimaging of alpha4beta2 nicotinic acetylcholine receptors in human. In this study the biokinetic of the (+) enantiomer was studied first time into humans. To assess the radiation risk by this new radioligand the biodistribution, organ doses (OD) and the effective dose (ED) were determined in 3 healthy volunteers. The results will be compared to the preclinical (mice: PET/MR piglets: PET/CT) and clinical (PET/CT) data and to the (-) enantiomer of flubatine [1].
Methods :
Whole body dosimetry was performed in 3 healthy volunteers (2 m, 1 f ; age: 58.3±5.8 y weight: 80.7±5.5 kg). The volunteers were sequentially PET-imaged up to 7h post i.v. injection of 285±13 MBq on a SIEMENS Biograph16 PET/CT-system on 9 bed positions (BP) per frame, 1.5 to 6 min/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). 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 [µSv/MBq] was received by urinary bladder (102.0 ± 29.6) and liver (53.1±29.8). The highest contribution to the ED [µSv/MBq] was by urinary bladder (4.1±1.2) and lungs (3.2±0.3). The estimated ED in humans is 23.0±1.9.
Conclusions :
The overall radiation risk was calculated to be 6.9 mSv/300MBq which is almost identically with the results of the (-)-enantiomer in humans (7.02 mSv/MBq). This is in the same magnitude as for other ¹⁸F labeled compounds too. Furthermore, the underestimation of the ED to humans based on preclinical data as mentioned in [1] could be verified for mice (12.1 µSv/MBq) and piglets (14.3 µSv/MBq) with this tracer too. This supports the use of animal image derived data for preclinical dose assessment to humans taking into account an underestimation of about 40%.
However, the risk assessment shown in this study encourages to transfer (+)-[18F]flubatine into further clinical study phases and further develop it as a clinical tool for PET brain imaging.