Radiosynthesis and biological evaluation of 123I-(±)-trans-2-hydroxy-5-((E)- -3-(iodo)allyloxy)-3-(4-phenyl-1-piperazinyl) tetralin

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

Abstrakty

This work reports both the radiolabeling and preliminary biodistribution results in the rat brains of (±)-[123I]- -II. The novel benzovesamicol derivative (±)-[123I]-II was successfully labeled with iodine-123 from its corresponding n-tributyltin, with radiochemical purity greater than 97% and radiochemical yield in the range 50–55%. (±)-[123I]-II showed a higher accumulation in striatum than in the other regions studied. To determine if (±)-[123I]-II could provide an advantage compared to reference compound [125I]-IBVM a kinetic study was carried out, at each point of the kinetic study, (±)-[123I]-II showed a lower specific binding compared to [125I]-IBVM. Time activity curves of (±)-[123I]-II confirmed that this compound is inferior to [125I]-IBVM to explore the VAChT in vivo by SPECT. 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; brain biodistribution; injected dose (ID); radioiodination; vesamicol derivatives; vesicular acetylcholine transporter (VAChT)

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2012
• Tom: Vol. 57, No. 1
• Strony: 75--80
• Opis fizyczny: Bibliogr. 12 poz., rys.

Twórcy

autor

Assaad T.

autor

Al Rayyes A. H.

Bibliografia

• 1. Assaad T (2011) Synthesis and characterization of novel benzovesamicol analogs. Turk J Chem 35:189–200
• 2. Assaad T, Mavel S, Emond P et al. (2007) Synthesis and ex vivo evaluation of aza-trozamicol analogs as SPECT radiotracers for exploration of the vesicular acetylcholine transporter. J Labelled Compd Radiopharm 50:139–14
• 3. Auld DS, Kornecook TJ, Bastianetto S, Quirion R (2002) Alzheimer’s disease and the basal forebrain cholinergic
• system: relations to beta-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 68:209–245
• 4. Bando K, Naganuma T, Taguchi K et al. (2000) Piperazine analog of vesamicol: in vitro and in vivo characterization for vesicular acetylcholine transporter. Synapse 38:27–37
• 5. Emond P, Mavel S, Zea-Ponce Y et al. (2007) (E)-[125I]-5-AOIBV: a SPECT radioligand for the vesicular acetylcholine transporter. Nucl Med Biol 34:967–971
• 6. Jung YW, Frey KA, Mulholland GK et al. (1996) Vesamicol receptor mapping of brain cholinergic neurons with radioiodine-labeled positional isomers of benzovesamicol. J Med Chem 39:3331–3342
• 7. Jung YW, Van Dort ME, Gildersleeve DL, Wieland DM (1990) A radiotracer for mapping cholinergic neurons of the brain. J Med Chem 33:2065–2068 8. Kuhl DE, Minoshima S, Fessler JA et al. (1996) In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 40:399–410
• 9. Mulholland GK, Jung YW (1992) Improved synthesis of [11C]methylamino-benzovesamicol. J Labelled Compd Radiopharm 31:253–259
• 10. Mulholland GK, Jung YW, Wieland DM, Kilbourn MR, Kuhl DE (1993) Synthesis of [18F]-fluoroethoxybenzovesamicol, a radiotracer for cholinergic neurons. J Labelled Compd Radiopharm 33:589–591
• 11. Parsons SM, Bahr BA, Rogers GA, Clarkson ED, Noremberg K, Hicks BW (1993) Acetylcholine transporter-vesamicol receptor pharmacology and structure. Prog Brain Res 98:175–181
• 12. Rogers GA, Parsons SM, Anderson DC et al. (1989) Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogues of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol). J Med Chem 32:1217–1230
• 13. Sorger D, Schliebs R, Kampfer I et al. (2000) In vivo [125I]-iodobenzovesamicol binding reflects corticalcholinergic deficiency induced by specific immunolesion of rat basalforebrain cholinergic system. Nucl Med Biol 27:23–31
• 14. Van Dort ME, Jung YW, Gildersleeve DL, Hagen CA, Kuhl DE, Wieland DM (1993) Synthesis of the 123I- and 125I-labeled cholinergic nervemarker (-)-5-iodobenzovesamicol. Nucl Med Biol 20:929–937
• 15.Zea-Ponce Y, Mavel S, Assaad T et al. (2005) Synthesis and in vitro evaluation of new benzovesamicol analogues as potential imaging probes for the vesicular acetylcholine transporter. Bioorg Med Chem 13:745–753