Preclinical Incorporation Dosimetry of (+)-[F-18]flubatine

Abstract:

Ziel: (+)-[F-18]flubatine is a new tracer for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk after intravenous application of the radioligand, the biodistribution, organ doses (OD) and the effective dose (ED) were assessed in pigs and compared to results based on data using the stereoisomere (-)-[F-18]flubatine.

Methodik: Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg) The animals were narcotized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq (+)-[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. 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-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103.

Ergebnisse: The highest OD was received by the urinary bladder (71.7±26.3µSv/MBq), the kidneys (45.1±6.5 µSv/MBq) and the brain (32.3±3.24µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9±1.1 µSv/MBq), the lungs (1.7±0.02µSv/MBq) and the red marrow (1.4±0.1µSv/MBq). According to this data, the ED to humans is 14.3±0.3 µSv/MBq.

Schlussfolgerungen: The effective dose upon i.v. application of about 300 MBq (+)-[F-18]flubatine to humans would be 7.1 mSv, taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%. This is well within the range of what is caused by other F18-labeled compounds to humans. This risk assessment encourages to transfer (+)-[F-18]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.