Preclinical PET/MRI – First time use and validation of a potential tool for image based dosimetry

Objectives :

PET image based preclinical dosimetry (ibPD) allows the dose assessment for new radiotracers. However, most of the small animal systems are combined with CT. The low soft tissue contrast results in poor organ delineation. Therefore, we like to evaluate a new preclinical PET/MRI system by comparing a recent ibPD in female mice (M) with a post mortem biodistribution (PMB) and previous PET/CT based studies in piglets (P) and humans (H), after i.v. injection of [¹⁸F]flubatine.

Methods :

Whole body ibPD was performed in 3 M (11 w, 27.8 g), 3 P (7 w, 14.0 kg) and 3 H (59.6 y, 74.3 kg). The anesthetized animals and the H were PET-imaged (M: MEDISO nanoScan PET/MRI; P, H: SIEMENS Biograph16 PET/CT) up to 7h post i.v. injection of 13.1 MBq, 183.5. MBq, 353.7 MBq [¹⁸F]flubatine, followed by iterative reconstruction including MR- and CT-based attenuation correction respectively. Exponential curves were fitted to the time-activity-data (%ID/organ). In M and P, time and mass were adapted to the human scale. The activity data from the PMB study was obtained by organ counting of 27 M (11 w, 28.2 g) in a γ-counter. The ODs were calculated with OLINDA and the ED using tissue weighting factors (ICRP103).

Results:

Based on preclinical PET/MRI, the highest OD (μSv/MBq) was in kidneys (47.5) and urinary bladder (33.4). The highest contribution to the ED (μSv/MBq) was by stomach (1.8) and lungs (1.7), resulting in an ED of 12.1 which is almost identical with the results of the PMB (12.5). The ED based on the PET/CT data is 14.3 (P) and 22.6 in H.

Conclusions :

It was proven, exemplary for [¹⁸F]flubatine, that ibPD studies with a preclinical PET/MRI in mice for dose assessment to humans are possible, taking into account an underestimation of the ED of about 40% as shown by earlier studies[1]. The investigation of further radiotracers is required to confirm the reliability of this study.

References:

[1] B. Sattler, M. Kranz, M. Patt et al. Incorporation dosimetry of F-18-Flubatine - Comparison of animal model data with first-in-man results. Journal of Nuclear Medicine 2012; 53(suppl): 1503.