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Chemical Delivery System of MIBG to the Central Nervous System: Synthesis, 11C‑Radiosynthesis, and in Vivo Evaluation

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journal contribution
posted on 15.02.2019, 00:00 by Fabienne Gourand, Delphine Patin, Axelle Henry, Méziane Ibazizène, Martine Dhilly, Fabien Fillesoye, Olivier Tirel, Mihaela-Liliana Tintas, Cyril Papamicaël, Vincent Levacher, Louisa Barré
The norepinephrine transporter (NET) plays an important role in neurotransmission and is involved in a multitude of psychiatric and neurodegenerative diseases. [123I/131I]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 1ad was synthesized, labeled with carbon-11, and evaluated in vivo into rats. The in vivo results demonstrated that, although adding substituents on CDS in 1ac 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.