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Molecules. 2018 Mar 20;23(3). pii: E702. doi: 10.3390/molecules23030702.

Bridging from Brain to Tumor Imaging: (S)-(-)- and (R)-(+)-[18F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice.

Author information

1
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany. m.kranz@hzdr.de.
2
Department of Diagnostic Radiology, PET Center, Yale University School of Medicine, New Haven, CT 06519, USA. m.kranz@hzdr.de.
3
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany. r.bergmann@hzdr.de.
4
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany. t.kniess@hzdr.de.
5
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany. b.belter@hzdr.de.
6
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany. c.neuber@hzdr.de.
7
Department of Diagnostic Radiology, PET Center, Yale University School of Medicine, New Haven, CT 06519, USA. zhengxin.cai@yale.edu.
8
Department of Neurosurgery and Biomedical Engineering, Yale University School of Medicine, New Haven, CT 06519, USA. gang.deng@yale.edu.
9
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany. s.fischer@hzdr.de.
10
Department of Neurosurgery and Biomedical Engineering, Yale University School of Medicine, New Haven, CT 06519, USA. jiangbing.zhou@yale.edu.
11
Department of Diagnostic Radiology, PET Center, Yale University School of Medicine, New Haven, CT 06519, USA. henry.huang@yale.edu.
12
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany. p.brust@hzdr.de.
13
Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 04318 Leipzig, Germany. w.deuther-conrad@hzdr.de.
14
Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany. j.pietzsch@hzdr.de.
15
Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, 01062 Dresden, Germany. j.pietzsch@hzdr.de.

Abstract

Sigma-1 receptors (Sig1R) are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET) can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S)-(-)- and (R)-(+)-[18F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously) implanted tumors. Therefore, a brain tumor model (U87-MG) with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [18F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB).

KEYWORDS:

[18F]fluspidine; carcinoma; dedicated small animal PET/CT; glioblastoma; melanoma; sigma-1 receptor

PMID:
29558382
PMCID:
PMC6017399
DOI:
10.3390/molecules23030702
[Indexed for MEDLINE]
Free PMC Article

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