First-in-man incorporation dosimetry of (S)-(-)-[18F]fluspidine

Objectives: (S)-(-)-[18F]fluspidine has been pre-clinically proven to be a distinctive radioligand for imaging 1-receptors with PET [1]. In this study, the biokinetics was studied first 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 4 healthy volunteers (2m, 2f; age: 22.5±2.7y weight: 62.5±8.4.5kg). They were sequentially PET/CT-imaged up to 7h post i.v. injection of 264±17 MBq, 8 bed positions (BP) per frame, 1.5 to 6 min/BP, followed by CT-attenuation correction and iterative reconstruction. All micturated urine was collected up to 7 hours post injection. Urine was weighed and samples measured for radioactivity concentration [Bq/ccm] in a well counter. 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 stylized adult male model as implemented in OLINDA v1. The ED was calculated using tissue weighting factors as published in ICRP60 and 103.
Results: The highest OD [µSv/MBq] was received by the liver (76.0±17.7), the gall bladder wall (60.7±10.6) and the small intestine (56.9±10.6). The highest contribution to the ED [µSv/MBq] was by the stomach wall (3.8±0.4), the lungs (3.4±0.3) and the liver (3.0±0.4). The conversion factor [µSv/MBq] to estimate the ED to humans is 22.1±1.3 (ICRP60) and 21.0±1.3 (ICRP103), respectively.
Conclusions: The effective dose was calculated to be 6.3 mSv/300MBq. This is in the order of magnitude as for other 18F-labeled PET-compounds. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging 1-receptors.
References:
[1] Brust P, Deuther-Conrad W, Becker G, Patt M, Donat CK, Stittsworth S, Fischer S, Hiller A, Wenzel B, Dukic-Stefanovic S, Hesse S, Steinbach J, Wunsch B, Lever SZ, and Sabri O (2014) Distinctive in vivo kinetics of the new sigma1 receptor ligands (R)-(+)- and (S)-(-)-18F-fluspidine in porcine brain. J Nucl Med 55[10], 1730-1736.