Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science

Synthesis and Radiolabelling of Ipratropium and Tiotropium for Use as PET Ligands in the Study of Inhaled Drug Deposition

Fatiah Issa A , Michael Kassiou A B C , Hak-Kim Chan D and Malcolm D. McLeod A E

A School of Chemistry, F11, University of Sydney, Sydney NSW 2006, Australia.

B Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Camperdown NSW 2050, Australia.

C Department of Pharmacology, D06, University of Sydney, Sydney NSW 2006, Australia.

D Faculty of Pharmacy, A15, University of Sydney, Sydney NSW 2006, Australia.

E Corresponding author. Email:

Australian Journal of Chemistry 59(1) 53-58
Submitted: 4 November 2005  Accepted: 30 November 2005   Published: 31 January 2006


Ipratropium bromide [(1R,3r,5S,8r,2′RS)-3-(3′-hydroxy-2′-phenylpropionyloxy)-8-isopropyl-8-methyl-8-azabicyclo[3.2.1]octan-8-ium bromide] and tiotropium bromide [(1R,2R,4S,5S,7s)-7-[2′-hydroxy-2′,2′-di(thiophen-2′′-yl)acetoxy]-9,9-dimethyl-9-aza-3-oxatricyclo[,4]nonan-9-ium bromide] are inhaled drugs used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Tertiary amine precursors have been synthesized and radiolabelled with carbon-11 by N-alkylation with [11C]CH3I. The [11C]ipratropium and [11C]tiotropium positron emission tomography (PET) ligands are obtained with high radiochemical purity, in 0.3 and 0.5% non-decay corrected yields based on [11C]CO2 at end-of-synthesis and specific activities of 11 and 18 GBq μmol-1, respectively, calculated at end-of-synthesis. These PET radioligands can be used in the study of inhaled drug deposition.


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