Radiosynthesis and evaluation of novel histamine H3 tracers

Champion, S. , Lewis, D., Dewar, D. , Honey, G., Gross, J., Robichaud, A., Welch, A., Wyper, D. and Pimlott, S. (2009) Radiosynthesis and evaluation of novel histamine H3 tracers. Eighteenth International Symposium on Radiopharmaceutical Sciences, Edmonton, Canada, 12 – 17 Jul 2009. S381. (doi: 10.1002/jlcr.1646)

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Abstract

Objectives: The histamine H3 receptor is thought to be implicated in numerous neurological and psychological disorders including Alzheimer’s disease and attention-deficit hyperactivity disorder. We are working in collaboration with the pharmaceutical industry to develop a single photon emission computed tomography (SPECT) brain imaging radiolabelled tracer for the H3 receptor in order to facilitate the development of selective histamine H3 antagonists as novel treatments for these disorders. Methods: The tracer candidates were identified from a library of compounds that have high affinity for the histamine H3 receptor. The radiosynthesis of three lead compounds was investigated, via iododestannylation and iododesilylation with radioiodide, for SPECT imaging. The Kd and Bmax of the radiolabelled compounds were determined in vitro in rat brain tissue. Results: All three compounds were successfully radiolabelled with an isolated radiochemical yield of greater than 39% and a radiochemical purity of greater than 99%. The stability of the isolated 125I-labelled compounds is such that the radiochemical purity is >95% after three days. The results from the in vitro evaluation of the all three candidates in rat brain will be presented. Conclusions: Further investigation of the lead candidate using in vivo animal imaging studies aims to determine the suitability of the tracer as a clinical imaging tool, which could then be used as biomarker of drug action in vivo.

Item Type:Conference or Workshop Item
Additional Information:Abstract of poster presentation - list of abstracts available in Journal of Labelled Compounds and Radiopharmaceuticals 52(S1): S381
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Pimlott, Dr Sally and Lewis, Dr David and Champion, Dr Sue and Dewar, Dr Deborah
Authors: Champion, S., Lewis, D., Dewar, D., Honey, G., Gross, J., Robichaud, A., Welch, A., Wyper, D., and Pimlott, S.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Labelled Compounds and Radiopharmaceuticals
ISSN:0362-4803

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