Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 10, Issue 3, Pages 352-357Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.8b00642
Keywords
Central nervous system; norepinephrine transporter; MIBG; radiosynthesis; redox chemical delivery system; 1,4-dihydroquinolines carriers
Categories
Funding
- CEA (Commissariat a l'Energie Atomique et aux Energies Alternatives)
- Labex IRON [ANR-11 LABX-0018-01]
- INSA-Rouen
- CNRS
- Labex SynOrg [ANR-11-LABX-0029]
- Region Normandie
- grant CIFRE from Region Basse-Normandie
- Cyclopharma laboratories
- Region Haute-Normandie [CRUNCh 6-13]
- Rouen University
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The norepinephrine transporter (NET) plays an important role in neurotransmission and is involved in a multitude of psychiatric and neurodegenerative diseases. [I-123/(13I)]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 la 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 la c is of no benefit for brain delivery of MIBG, the presence of a linker in CDS-MIBG ld greatly improved both brain penetration and the release rate of MIBG in the central nervous system.
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