Preclinical small animal PET/MRI for radiopharmaceutical dosimetry

Aim
To assess the radiation risk after injection of new PET radiotracers small animal PET/MRI provides the essential whole body biodistribution data for image based dosimetry (ibD). In this study, we investigate ((S)-(-)^# and (R)-(+)^##-[¹⁸F]fluspidine, a PET radioligand for neuroimaging of σ1 receptors in mice. Organ doses (OD) and the effective dose (ED) were determined using PET/MR ibD to assess the radiation risk to humans. The results will be compared to those previously acquired for (-)-^*and (+)-^** [¹⁸F]flubatine , to proof the concept of small animal PET/MRI for incorporation dosimetry to assess the radiation exposure to humans by radiopharmaceuticals.

Materials and methods
Six female CD1 mice (weight: 30.9±1.3 g) were injected i.v. with 13.2±3.0 MBq (#, n=3) or 12.6±1.4 MBq (##, n=3), respectively. A dynamic 2 h animal PET/MRI protocol was performed (MEDISO nanoScan^®, Hungary). All relevant organs were defined by volumes of interest. Time- and mass-scales were adapted to the human anatomy; exponential curves were fitted to the time-activity-data (%ID/organ). The ODs were computed using the adult male model with OLINDA and the ED using tissue weighting factors (ICRP103). The results were compared to previously acquired data of post mortem biodistribution (PMB) studies in mice for (-)-[¹⁸F]flubatine (n=27, Ø28.2 g) and [¹⁸F]fluspidine (n=28#/n=22##, Ø29.6 g).

Results
The excreting organs (kidneys, liver and urinary bladder) received the highest ODs. Subsequently, these organs provide the largest contribution to the ED. The overall radiation risk to humans based on animal biodistribution data acquired with ibD would be 12.9# and 14.0## (16.7#; 18.4## based on PMB). Comparable results were estimated for [¹⁸F]flubatine: 12.5*(PMB), 12.1**.

Conclusion
ibD of [¹⁸F]fluspidine reveals major differences between the two enantiomers. The tracer with higher affinity and slower kinetics (^##) causes a higher radiation exposure than its enantiomeric counterpart (^#) both in ibD and PMB. Furthermore, the ibD shows lower ED values compared to the PMB due to the intrinsic methodological differences. Small animal ibB is feasible and its reliability needs to be further investigated and confirmed.