[ ¹⁸F]FMeNER-D2

Author(s)

Christina Rami-Mark, Nadine Eberherr, Neydher Berroteran-Infante, Thomas Vanicek, Lukas Nics, Rupert Lanzenberger, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser

Abstract

Introduction The norepinephrine transporter (NET) presents an important target for therapy and diagnosis of ADHD and other neurodegenerative and psychiatric diseases. Thus, PET is the diagnostic method of choice, using radiolabeled NET-ligands derived from reboxetine. So far, [

¹⁸F]FMeNER-D2 showed best pharmacokinetic and -dynamic properties. However, the disadvantage of reboxetine derived PET tracers is their high metabolic cleavage—resulting in impeding signals in the PET scans, which hamper a proper quantification of the NET in cortical areas. Methods Metabolic stability testing was performed in vitro using a plethora of human and murine enzymes. Results No metabolism was observed using monoamine oxidase A and B or catechol-O-methyl transferase. Incubation of [

¹⁸F]FMeNER-D2 with CYP450-enzymes, predominantly located in the liver, led to a significant and fast metabolism of the tracer. Moreover, the arising three radiometabolites were found to be more polar than [

¹⁸F]FMeNER-D2. Surprisingly, definitely no formation of free [

¹⁸F]fluoride was observed. Conclusion According to our in vitro data, the interfering uptake in cortical regions might be attributed to these emerging radiometabolites but does not reflect bonding in bone due to defluorination. Further research on these radiometabolites is necessary to elucidate the in vivo situation. This might include an analysis of human blood samples after injection of [

¹⁸F]FMeNER-D2, to enable a better correction of the PET-input function.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

Medizinische Universität Wien

Journal

Nuclear Medicine and Biology

Volume

43

Pages

490-495

No. of pages

6

ISSN

0969-8051

DOI

https://doi.org/10.1016/j.nucmedbio.2016.05.004

Publication date

08-2016

Peer reviewed

Yes

Austrian Fields of Science 2012

301304 Medical biology, 302054 Nuclear medicine

Keywords

ASJC Scopus subject areas

Molecular Medicine, Radiology Nuclear Medicine and imaging, Cancer Research

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/f9f1f823-6c93-493a-a8a8-5e799e0d0720