Fully Automated Synthesis of Novel TSPO PET Imaging Ligand [18F]Fluoroethyltemazepam.

Dario Fiorenza,Ferdinando Fiorino,Carlo Cavaliere,Giovanna Esposito,Emanuele Nicolai,Marco Salvatore

doi:10.3390/molecules26082372

Abstract

Introduction: Benzodiazepines, including temazepam are described as TSPO antagonists. In fact, TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam. TSPO is a potential imaging target of neuroinflammation because there is an amplification of the expression of this receptor. Objectives: Herein, we developed a novel fluorinated benzodiazepine ligand, [18F]Fluoroethyltemazepam ([18F]F-FETEM), for positron emission tomography (PET) imaging of translocator protein (18 kDa). Methods: [18F]F-FETEM was radiolabelled with an automated synthesizer via a one-pot procedure. We conducted a [18F]F-aliphatic nucleophilic substitution of a tosylated precursor followed by purification on C18 and Alumina N SPE cartridges. Quality control tests was also carried out. Results: We obtained 2.0–3.0% decay-uncorrected radiochemical activity yield (3.7% decay-corrected) within the whole synthesis time about 33 min. The radiochemical purity of [18F]F-FETEM was over 90% by TLC analysis. Conclusions: This automated procedure may be used as basis for future production of [18F]F-FETEM for preclinical PET imaging studies.

Highlights

Context and background: Translocator protein TSPO is a protein located on the outer mitochondria membrane mainly expressed in the brain in glial cells
TSPO was initially described as a peripheral benzodiazepine receptor (PBR) with a secondary binding site for diazepam; subsequent research has found that this receptor is expressed throughout whole body
Experimental approach/major findings: In this paper, we introduce a new type of TSPO radiotracer (3S)-7-chloro-3-[18 F]fluoroethyl-1-methyl-5-phenyl-3H-1,4-benzodiazepin2-one, [18 F]Fluoroethyltemazepam ([18 F]F-FETEM) radiolabelled with an automated synthesizer via a one-pot procedure

Summary

Introduction

Context and background: Translocator protein TSPO is a protein located on the outer mitochondria membrane mainly expressed in the brain in glial cells. Mitochondria are involved in several vital and detrimental processes and mitochondrial dysfunctions are related in a variety of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and psychiatric condition such as anxiety and bipolar disorder [1]. Translocator protein is encoded by the TSPO gene and belongs to the tryptophan-rich family of sensory proteins [2]. TSPO-binding ligands showed influence in a variety of cellular functions TSPO increase expression was found in activated microglia during neuroinflammation and immunosuppressive action of the TSPO ligands make TSPO an attractive target for diagnostic imaging [6]

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