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

Objectives (-)-[¹⁸F]flubatine is successfully used for neuroimaging of alpha4beta2 nicotinic acetylcholine receptors in humans [SATTLER JNM2014]. In this study, the biokinetics of the (+)-enantiomere was studied first time in man. To assess the radiation risk, the biodistribution, organ doses (OD) and the effective dose (ED) were determined.

Methods Whole body dosimetry was performed in 3 healthy volunteers (2m; age: 58.3±5.8y weight: 80.7±5.5 kg). They were sequentially PET/CT-imaged up to 7h post i.v. injection of 285±13 MBq, 9 bed positions (BP) per frame, 1.5 to 6 min/BP, followed by 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/organ). The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in ICRP103.

Results The highest OD [µSv/MBq] was received by the urinary bladder (102.0 ± 29.6) and the liver (53.1±29.8). The highest contribution to the ED [µSv/MBq] was by the urinary bladder (4.1±1.2) and the lungs (3.2±0.3). The estimated ED in humans is 23.0±1.9µSv/MBq.

Conclusions The radiation risk was calculated to be 6.9 mSv/300MBq. This is in the order of magnitude as for the (-)-enantiomer or other ¹⁸F-labeled PET-compounds. Furthermore, the general underestimation of the ED to humans based on preclinical data, as shown in a previous study for mice (12.1 µSv/MBq) and piglets (14.3 µSv/MBq), could be confirmed for this tracer. The fact that the use of preclinical data to assess the radiation exposure to humans underestimates this dose by about 40% was also found for (+)-[¹⁸F]flubatine. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging of alpha4beta2 nicotinic acetylcholine receptors in brain diseases.

Research Support The trial is funded by Helmholtz Validation Fonds and partially co-funded by Strahlenschutzseminar in Thüringen (Project-Code F2010-10)