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

Objectives (S)-(-)-[18F]Fluspidine has been pre-clinically proven to be a highly selective radioligand for imaging σ1 receptors with PET [1, 2]. 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 (2 male, 2 female; age: 22.5 ± 2.7 y weight: 62.5±8.4 kg). They were sequentially PET/CT-imaged up to 7 h 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 h p.i. Urine was weighed and samples measured for radioactivity concentration [Bq/ccm] in a well counter. PET data analysis was done by defining all relevant organs by volumes of interest that considerably accumulated the tracer. Exponential curves were fitted to the time-activity data (%ID/organ vs. time p.i.). The ODs were calculated using OLINDA v1. The ED was calculated using tissue weighting factors as published in ICRP60 and -103.

Results The fraction of radioactivity that was eliminated via urine was 25 ± 10%. 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 6,6 mSv/MBq (ICRP60) and 6.3 mSv/300MBq (ICRP103), respectively. This is in the order of magnitude as for other 18F-labeled PET tracers. The results provide a rationale for further clinical study phases and the development of this tracer as a clinical tool for PET imaging σ1 receptors.