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

Objectives : (+)-[¹⁸F]flubatine is the mirror image isomer of (-)-[¹⁸F]flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs in human. To assess the radiation risk by this new radioligand, biodistribution, organ doses (OD) and the effective dose (ED) were determined in piglets.

Methods : Whole body dosimetry was performed in 3 female piglets (age: 43±1.2d, weight: 14±1.0kg). The animals were anesthetized and sequentially PET-imaged up to 5h post i.v. injection of 183.5±9.0MBq on a SIEMENS Biograph16 PET/CT-system on 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.

Results : The highest OD [µSv/MBq] was received by urinary bladder (71.7±26.3) and kidneys (45.1±6.5). The highest contribution to ED [µSv/MBq] was by urinary bladder (2.9±1.1) and lungs (1.7±0.02). The estimated ED to humans is 14.3±0.3.

Conclusions : Considering 40% underestimation of the ED to humans by preclinical dosimetry [1], the expected ED to humans after 300MBq i.v. is 7.2 mSv, which is about the ED by (-)-[¹⁸F]flubatine (6.8 mSv/300MBq) and well within the range of what other F-18-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[¹⁸F]flubatine from preclinical to clinical study phases and to further develop as a clinical tool for PET imaging of the brain.

[1] Sattler B, …, Sabri O. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. J. Nucl. Med. 2012; 53(suppl): 1503.

Research Support: The trial is partly co-funded by Strahlenschutzseminar in Thüringen e.V. and by Helmholtz Validation Fonds.