(R)-[18F]NEBIFQUINIDE: A promising new PET tracer for TSPO imaging

Neydher Berroterán-Infante; Thomas Kalina; Lukas Fetty; Victoria Janisch; Ramona Velasco; Chrysoula Vraka; Marcus Hacker; Alexander R Haug; Katharina Pallitsch; Wolfgang Wadsak; Markus Mitterhauser

doi:10.1016/j.ejmech.2019.05.008

(R)-[¹⁸F]NEBIFQUINIDE: A promising new PET tracer for TSPO imaging

Eur J Med Chem. 2019 Aug 15:176:410-418. doi: 10.1016/j.ejmech.2019.05.008. Epub 2019 May 10.

Affiliations

¹ Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria.
² Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
³ Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
⁴ Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria. Electronic address: katharina.pallitsch@univie.ac.at.
⁵ Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria; Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria; Center for Biomarker Research, CBmed, Stiftingtalstraße 5, 8010, Graz, Austria. Electronic address: wolfgang.wadsak@meduniwien.ac.at.
⁶ Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria; Ludwig Boltzmann Institute Applied Diagnostics, Währinger Gürtel 18-20, 1090, Vienna, Austria.

PMID: 31125895
DOI: 10.1016/j.ejmech.2019.05.008

Abstract

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), has a high diagnostic potential in neurodegenerative disorders and cancer. However, TSPO is considered a challenge for molecular imaging due to the poor availability of suitable radiotracers with adequate pharmacokinetic properties. Here, we describe the development of a radiofluorinated pyridinyl isoquinoline analogue of the established TSPO PET tracer (R)-[¹¹C]PK11195 with improved binding properties in all known human TSPO phenotypes. We conducted a complete preclinical evaluation using in vitro, in vivo and ex vivo methods to assess the performance of this novel radiotracer and observed high specific binding of the radiotracer to TSPO, as well as high metabolic stability. Therefore, we propose this radiolabeled compound for further evaluation in animal models as well as in clinical trials.

Keywords: Fluorine-18; Imaging agents; Preclinical evaluation; Radiopharmaceuticals; TSPO.

MeSH terms

Animals
Female
Fluorine Radioisotopes / chemistry
Humans
Isoquinolines / chemical synthesis
Isoquinolines / chemistry
Isoquinolines / metabolism*
Isoquinolines / pharmacokinetics
Isotope Labeling
Mice, Inbred C57BL
Microsomes, Liver / metabolism
Positron-Emission Tomography / methods
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / metabolism*
Pyridines / pharmacokinetics
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry
Radiopharmaceuticals / metabolism*
Radiopharmaceuticals / pharmacokinetics
Receptors, GABA / metabolism*
Tissue Distribution

Substances

Bzrp protein, mouse
Fluorine Radioisotopes
Isoquinolines
Pyridines
Radiopharmaceuticals
Receptors, GABA
Fluorine-18