Open AccessChemical Delivery System of MIBG to the Central Nervous System: Synthesis, 11C-Radiosynthesis, and in Vivo Evaluation
Author(s) -
Fabienne Gourand,
Delphine Patin,
Axelle Henry,
Méziane Ibazizène,
Martine Dhilly,
Fabien Fillesoye,
O. Tirel,
Mihaela-Liliana Ţînţaş,
Cyril Papamicaël,
Vincent Levacher,
Louisa Barré
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.8b00642
Subject(s) - in vivo , radiosynthesis , linker , chemistry , norepinephrine , central nervous system , moiety , norepinephrine transporter , pharmacology , combinatorial chemistry , neuroscience , medicine , biology , stereochemistry , computer science , dopamine , microbiology and biotechnology , operating system
The norepinephrine transporter (NET) plays an important role in neurotransmission and is involved in a multitude of psychiatric and neurodegenerative diseases. [ 123 I/ 131 I] meta -iodobenzylguanidine (MIBG) is a widely used radiotracer in the diagnosis and follow-up of peripheral neuroendocrine tumors overexpressing the norepinephrine transporter. MIBG does not cross the blood-brain barrier (BBB), and we have demonstrated the "proof-of-concept" that 1,4-dihydroquinoline/quinolinium salt as chemical delivery system (CDS) is a promising tool to deliver MIBG to the brain. To improve BBB passage, various substituents on the 1,4-dihydroquinoline moiety and a linker between CDS and MIBG were added. A series of CDS-MIBG 1a - d was synthesized, labeled with carbon-11, and evaluated in vivo into rats. The in vivo results demonstrated that, although adding substituents on CDS in 1a - c is of no benefit for brain delivery of MIBG, the presence of a linker in CDS-MIBG 1d greatly improved both brain penetration and the release rate of MIBG in the central nervous system.