Fiorenza, Dario (2022) Sintesi automatizzata del nuovo ligando per TSPO PET imaging [18F]Fluoroetiltemazepam e metodologia di nanoincapsulazione in matrici lipidiche. [Tesi di dottorato]

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Abstract

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. Herein, we developed a novel fluorinated benzodiazepine ligand, [18F]Fluoroethyltemazepam ([18F]F-FETEM), for positron emission tomography (PET) imaging of translocator protein (18 kDa). [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. 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. This automated procedure may be used as basis for future production of [18F]F-FETEM for preclinical PET imaging studies. As regards the possible methodology of encapsulation of [18F]-fluoroethyltemazepam radioligand in nanocarriers, a strategy of functionalization of complex lipid derivatives of phosphoethanolamine, whose polar head containing the -NH2 group can react with the FDG forming a Amadori product not complete, through a Maillard reaction. The compound synthesized according to this reaction scheme, which constitutes the external skeleton of the self-assembling nanocarrier, is FDG-18: 1 Caproylamina PE.

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