Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [18F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ1 Receptors
Mathias Kranz,
Bernhard Sattler,
Nathanael Wüst,
Winnie Deuther-Conrad,
Marianne Patt,
Philipp M. Meyer,
Steffen Fischer,
Cornelius K. Donat,
Bernhard Wünsch,
Swen Hesse,
Jörg Steinbach,
Peter Brust,
Osama Sabri
Affiliations
Mathias Kranz
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Bernhard Sattler
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
Nathanael Wüst
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
Winnie Deuther-Conrad
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Marianne Patt
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
Philipp M. Meyer
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
Steffen Fischer
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Cornelius K. Donat
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Bernhard Wünsch
Pharmaceutical and Medicinal Chemistry, University Münster, Münster 48149, Germany
Swen Hesse
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
Jörg Steinbach
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Peter Brust
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
Osama Sabri
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
The enantiomers of [18F]fluspidine, recently developed for imaging of σ1 receptors, possess distinct pharmacokinetics facilitating their use in different clinical settings. To support their translational potential, we estimated the human radiation dose of (S)-(−)-[18F]fluspidine and (R)-(+)-[18F]fluspidine from ex vivo biodistribution and PET/MRI data in mice after extrapolation to the human scale. In addition, we validated the preclinical results by performing a first-in-human PET/CT study using (S)-(−)-[18F]fluspidine. Based on the respective time-activity curves, we calculated using OLINDA the particular organ doses (ODs) and effective doses (EDs). The ED values of (S)-(−)-[18F]fluspidine and (R)-(+)-[18F]fluspidine differed significantly with image-derived values obtained in mice with 12.9 μSv/MBq and 14.0 μSv/MBq (p < 0.025), respectively. A comparable ratio was estimated from the biodistribution data. In the human study, the ED of (S)-(−)-[18F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [18F]fluspidine enantiomers determined from the preclinical studies are comparable with other 18F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(−)-[18F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(−)-[18F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies.