Synthesis and labeling of a piperazine-based library of C-11-labeled ligands for imaging of the vesicular acetylcholine transporter
2014 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, no 8, 525-532 p.Article in journal (Refereed) Published
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, [C-11]-(+/-)5a-f, were C-11-labeled by a palladium (0)-mediated aminocarbonylation, utilizing a standard protocol. The labeled compounds [C-11]-(+/-)5a-f were obtained in radiochemical purities >95% with decay-corrected radiochemical yields and specific radioactivities between 4-25% and 124-597 GBq/mu mol, respectively. Autoradiography studies were then conducted to assess the compounds binding selectivity for VAChT. Labeled compounds [C-11]-(+/-)5d and [C-11]-(+/-)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.
Place, publisher, year, edition, pages
2014. Vol. 57, no 8, 525-532 p.
vesicular acetylcholine transporter, carbonylation, PET, library, C-11-labeling, vesamicol
Radiology, Nuclear Medicine and Medical Imaging Medicinal Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-231333DOI: 10.1002/jlcr.3208ISI: 000340169500004PubMedID: 24991704OAI: oai:DiVA.org:uu-231333DiVA: diva2:744191