Synthesis and biodistribution of both (±)-5-[ 18F]-fluoroethoxy and (±)-5-[ 18F]-fluoropropoxy piperazine analogs of benzovesamicol as vesicular acetylcholine transporter ligands (VAChT)

• Autorzy: Assaad T. , Al Rayyes A. H.
• Języki publikacji: EN

Abstrakty

EN

The radiosynthesis and preliminary biological evaluation in rats’ brain of two novel piperazine analogs of benzovesamicol as ligands for the vesicular acetylcholine transporter (VAChT) have been carried out. The novel benzovesamicol derivatives 5-(2-fluoroethoxy)-3-(4-phenylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol and 5-(3-fluoropropoxy)-3-(4-phenylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalen-2-ol [(±)-[18F]-6 and (±)-[18F]-7] were successfully labelled with fluorine-18 from their tosylate precursors, with radiochemical purities greater than 98% and with radiochemical yield in the range of 5–6%. To determine whether these compounds could have potential advantage compared to [125I]-iodo benzovesamicol (IBVM), IBVM was also labelled and used as the reference compound in all in vivo experiments. Both (±)-[18F]-6 and (±)-[18F]-7 showed lower specific binding in all brain areas explored 2 h post injection when compared to reference compound (-)-[125I] IBVM. Furthermore, defluorination indicated that (±)-[18F]-6 and (±)-[18F]-7 are not suitable as radioligands to explore the VAChT in vivo by PET. Moreover, it is well known that interaction at the VAChT binding site is enantioselective, and therefore, working with enantiomerically pure compounds, could improve the compound activity.

Słowa kluczowe

EN

Alzheimer's disease (AD); benzovisamicol derivatives; brain biodistribution; enantiomeric resolution; radiofluorination; vesicular acetylcholine transporter (VAChT)

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2013
• Tom: Vol. 58, No. 2
• Strony: 269--274
• Opis fizyczny: Bibliogr. 16 poz., rys.

Twórcy

autor

Assaad T.

• Department of Chemistry, Atomic Energy Commission of Syria (AECS), P. O. Box 6091, Damascus, Syrian Arab Republic, Tel.: [phone], Fax: [phone]

autor

Al Rayyes A. H.

• Department of Chemistry, Atomic Energy Commission of Syria (AECS), P. O. Box 6091, Damascus, Syrian Arab Republic, Tel.: [phone], Fax: [phone]

Bibliografia

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