Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [(18)F]Fluspidine-A New Tracer in Clinical Translation for Imaging of σ₁ Receptors.
The enantiomers of [(18)F]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)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]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)-(-)-[(18)F]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)-(-)-[(18)F]fluspidine and (R)-(+)-[(18)F]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)-(-)-[(18)F]fluspidine was calculated as 21.0 μSv/MBq. Altogether, the ED values for both [(18)F]fluspidine enantiomers determined from the preclinical studies are comparable with other (18)F-labeled PET imaging agents. In addition, the first-in-human study confirmed that the radiation risk of (S)-(-)-[(18)F]fluspidine imaging is within acceptable limits. However, as already shown for other PET tracers, the actual ED of (S)-(-)-[(18)F]fluspidine in humans was underestimated by preclinical imaging which needs to be considered in other first-in-human studies.
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. m.kranz@hzdr.de.
Mathias
M
Kranz
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Bernhard.Sattler@medizin.uni-leipzig.de.
Bernhard
B
Sattler
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Nathanael.Wuest@gmx.de.
Nathanael
N
Wüst
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. w.deuther-conrad@hzdr.de.
Winnie
W
Deuther-Conrad
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Marianne.Patt@medizin.uni-leipzig.de.
Marianne
M
Patt
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Philipp.Meyer@medizin.uni-leipzig.de.
Philipp M
PM
Meyer
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. s.fischer@hzdr.de.
Steffen
S
Fischer
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. c.donat@imperial.ac.uk.|Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London SW7 2AZ, UK. c.donat@imperial.ac.uk.
Cornelius K
CK
Donat
Pharmaceutical and Medicinal Chemistry, University Münster, Münster 48149, Germany. wuensch@uni-muenster.de.
Bernhard
B
Wünsch
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Swen.Hesse@medizin.uni-leipzig.de.|Integrated Research and Treatment Center (IFB) Adiposity Diseases, University Hospital Leipzig, Leipzig 04103, Germany. Swen.Hesse@medizin.uni-leipzig.de.
Swen
S
Hesse
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. j.steinbach@hzdr.de.
Jörg
J
Steinbach
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany. p.brust@hzdr.de.
Peter
P
Brust
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany. Osama.Sabri@medizin.uni-leipzig.de.
Osama
O
Sabri
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
C558383:1'-benzyl-3-(2-fluoroethyl)-3H-spiro((2)benzofuran-1,4'-piperidine); D001572:Benzofurans; D005462:Fluorine Radioisotopes; D010880:Piperidines; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals
[18F]fluspidine; image based internal dosimetry; preclinical hybrid PET/MRI; radiation safety; σ1 receptors