Home
Resources
Publications
Synthesis and Pharmacological Evaluation of [ 11 C]Granisetron and [ 18 F]Fluoropalonosetron as PET Probes for 5-HT 3 Receptor Imaging

Synthesis and Pharmacological Evaluation of [ 11 C]Granisetron and [ 18 F]Fluoropalonosetron as PET Probes for 5-HT 3 Receptor Imaging

Linjing Mu, Adrienne Müller Herde, Pascal M Rüefli, Filippo Sladojevich, Selena Milicevic Sephton, Stefanie D Krämer, Andrew J Thompson, Roger Schibli, Simon M Ametamey, Martin Lochner

ACS Chem Neurosci. 2016 Nov 16;7(11):1552-1564.

PMID: 27571447

Abstract:

Serotonin-gated ionotropic 5-HT3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril) and palonosetron (Aloxi), belong to a family of drugs (the "setrons") that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15) that has a binding affinity (Ki = 0.26 ± 0.05 nM) similar to the parent drug (Ki = 0.21 ± 0.03 nM). We radiolabeled 15 by nucleophilic 18F-fluorination of an unsymmetrical diaryliodonium palonosetron precursor and achieved the radiosynthesis of 1-(methyl-11C)-N-granisetron ([11C]2) through N-alkylation with [11C]CH3I, respectively. Both compounds [18F]15 (chemical and radiochemical purity >95%, specific activity 41 GBq/μmol) and [11C]2 (chemical and radiochemical purity ≥99%, specific activity 170 GBq/μmol) were evaluated for their utility as positron emission tomography (PET) probes. Using mouse and rat brain slices, in vitro autoradiography with both [18F]15 and [11C]2 revealed a heterogeneous and displaceable binding in cortical and hippocampal regions that are known to express 5-HT3 receptors at significant levels. Subsequent PET experiments suggested that [18F]15 and [11C]2 are of limited utility for the PET imaging of brain 5-HT3 receptors in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP135729769	Palonosetron Related Compound C		135729-76-9	Price
AP141136018	Granisetron Related Compound C		141136-01-8	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: