Thèse soutenue

Diagnostic précoce de la maladie d'Alzheimer : développement de médicaments radiopharmaceutiques iodés pour l'exploration scintigraphique en TEMP du transporteur vésiculaire de l'acétylcholine
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Accès à la thèse
Auteur / Autrice : Thaer Assaad
Direction : Denis Guilloteau
Type : Thèse de doctorat
Discipline(s) : Chimie
Date : Soutenance en 2006
Etablissement(s) : Tours

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Résumé

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One of the first aspect of Alzheimer disease is the dysfunction of the central cholinergic system, inducing the death of cholinergic neurons which involves a reduction in the density of the vesicular acetylcholine transporters (VAChT) localised in these neurons. The quantification of the density of the transporter makes it possible to help with early diagnosis as well as with the therapeutic follow-up of this desease. With this objective, we proposed to develop specific tracers to this transporter. This development rests on the choice of a chemical structure likely to have a strong affinity and selectivity for VAChT. From a literature search, the vesamicol family was chosen to develop our tracers. We chose some interesting compounds in this family (iodobenzovesamicol or IBVM, trozamicol and prezamicol) of which we modified the sturcture at certain places which appeared compatible to us with the recognition of the site of connection with the vacht in order to obtain a radiopharmaceutical usable in SPECT. We synthesized 30 analogues of vesamicol. All products were tested in vitro for their affinities for VAChT. Four compounds was selected for radiolabelling with iodine-125 followed by a biological validation (ex vivo).