Synthesis and labeling of a piperazine‐based library of 11 C‐labeled ligands for imaging of the vesicular acetylcholine transporter

• Published in: Journal of labelled compounds & radiopharmaceuticals 2014-06, Vol.57 (8), p.525-532
• Main Authors: Bergman, Sara, Estrada, Sergio, Hall, Håkan, Rahman, Rashidur, Blomgren, Andreas, Larhed, Mats, Svedberg, Marie, Thibblin, Alf, Wångsell, Fredrik, Antoni, Gunnar
• Format: Article
• Language: English
• Subjects: C-11-labeling; carbonylation; library; PET; vesamicol; vesicular acetylcholine transporter
• ISSN: 0362-4803; 1099-1344; 1099-1344
• DOI: 10.1002/jlcr.3208

The cholinergic system is involved in neurodegenerative diseases, and visualization of cholinergic innervations with positron emission tomography (PET) would be a useful tool in understanding these diseases. A ligand for the vesicular acetylcholine transporter (VAChT), acknowledged as a marker for cholinergic neurons, could serve as such a PET tracer. The aim was to find a VAChT PET tracer using a library concept to create a small but diverse library of labeled compounds. From the same precursor and commercially available aryl iodides 6a–f, six potential VAChT PET tracers, [ 11 C]‐(±)5a–f, were 11 C‐labeled by a palladium (0)‐mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [ 11 C]‐(±)5a–f were obtained in radiochemical purities >95% with decay‐corrected radiochemical yields and specific radioactivities between 4–25% and 124–597 GBq/µmol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [ 11 C]‐(±)5d and [ 11 C]‐(±)5e showed specific binding but not enough to permit further preclinical studies. To conclude, a general method for a facile synthesis and labeling of a small piperazine‐based library of potential PET tracers for imaging of VAChT was shown, and in upcoming work, another scaffold will be explored using this approach