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Molecules 2016, 21(9), 1164; doi:10.3390/molecules21091164

Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [18F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ1 Receptors

1
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Leipzig 04318, Germany
2
Department of Nuclear Medicine, University Hospital Leipzig, Leipzig 04103, Germany
3
Division of Brain Sciences, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London SW7 2AZ, UK
4
Pharmaceutical and Medicinal Chemistry, University Münster, Münster 48149, Germany
5
Integrated Research and Treatment Center (IFB) Adiposity Diseases, University Hospital Leipzig, Leipzig 04103, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Zhen Cheng
Received: 28 July 2016 / Revised: 22 August 2016 / Accepted: 26 August 2016 / Published: 1 September 2016
(This article belongs to the Special Issue Molecular Imaging Probes)
View Full-Text   |   Download PDF [949 KB, uploaded 1 September 2016]   |  

Abstract

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. View Full-Text
Keywords: image based internal dosimetry; [18F]fluspidine; preclinical hybrid PET/MRI; radiation safety; σ1 receptors image based internal dosimetry; [18F]fluspidine; preclinical hybrid PET/MRI; radiation safety; σ1 receptors
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Kranz, M.; Sattler, B.; Wüst, N.; Deuther-Conrad, W.; Patt, M.; Meyer, P.M.; Fischer, S.; Donat, C.K.; Wünsch, B.; Hesse, S.; Steinbach, J.; Brust, P.; Sabri, O. Evaluation of the Enantiomer Specific Biokinetics and Radiation Doses of [18F]Fluspidine—A New Tracer in Clinical Translation for Imaging of σ1 Receptors. Molecules 2016, 21, 1164.

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