Delivering FLT to the Central Nervous System by Means of a Promising Targeting System: Synthesis, [11C]Radiosynthesis, and in Vivo Evaluation

Fabienne Gourand (1) , Mihaela-Liliana Tîntas (1) , Axelle Henry (2) , Méziane Ibazizène (1) , Martine Dhilly (1) , Fabien Fillesoye (1) , Cyril Papamicaël (2) , Vincent Levacher (2) , Louisa Barré (1)

1 LDM-TEP - Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

The development of delivery systems to transport some specific radiotracers across the blood-brain barrier (BBB) needs to be investigated for brain imaging. [18F]FLT (3′-deoxy-3′-18F-fluoro-l-thymidine), an analogue substrate of the nucleoside thymidine, has been developed as a proliferation tracer for oncological PET studies. Unfortunately, low-grade brain tumors are poorly visualized due to the low uptake of [18F]FLT in brain tissue, preventing its use in PET imaging to detect brain tumors at an early stage. Based on our previous work, a redox chemical delivery system (CDS) related to Bodor’s strategy was developed to enable the penetration of FLT into the brain. To this end, FLT was covalently linked to a series of lipophilic carriers based on a 1,4-dihydroquinoline structure. To determine the best carrier, various sets of [11C]CDS-FLT were prepared and injected into rats. Pleasingly, in vivo results let us suggest that this CDS is a promising approach to overcome the BBB to target low-grade brain tumors for PET imaging.

Keywords: Chemical delivery system; Low grade glioma; PET imaging; Brain-targeted delivery system; [18F]FLT

Domains: Chemical Sciences

Fabienne Gourand, Mihaela-Liliana Tîntas, Axelle Henry, Méziane Ibazizène, Martine Dhilly, et al.. Delivering FLT to the Central Nervous System by Means of a Promising Targeting System: Synthesis, [11C]Radiosynthesis, and in Vivo Evaluation. ACS Chemical Neuroscience, 2017, 8 (11), pp.2457-2467. ⟨10.1021/acschemneuro.7b00218⟩. ⟨hal-02046279⟩