Journal
ACS CHEMICAL NEUROSCIENCE
Volume 8, Issue 11, Pages 2457-2467Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.7b00218
Keywords
Brain-targeted delivery system; chemical delivery system; low grade glioma; PET imaging; [F-18]FLT
Funding
- CEA (Commissariat a l'Energie Atomique et aux Energies Alternatives)
- LABEX IRON [ANR-11 LABX-0018-01]
- INSA-Rouen
- Rouen University
- CNRS
- Labex SynOrg [ANR-11-LABX-0029]
- Region Normandie
- Region Haute-Normandie [CRUNCh 6-13]
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The development of delivery systems to transport some specific radiotracers across the blood-brain barrier (BBB) needs to be investigated for brain imaging. [F-18]FLT (3'-deoxy-3'-F-18-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 [C-11]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.
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