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

Fatiah Issa; Michael Kassiou; Hak-Kim Chan; Malcolm D. McLeod

doi:10.1071/CH05303

RESEARCH ARTICLE

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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

+ Author Affiliations

- Author Affiliations

^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: m.mcleod@chem.usyd.edu.au

Australian Journal of Chemistry 59(1) 53-58 https://doi.org/10.1071/CH05303
Submitted: 4 November 2005 Accepted: 30 November 2005 Published: 31 January 2006

Abstract

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[3.3.1.0^2,4]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.

Acknowledgments

We thank Mr David Henderson for performing the irradiations, as well as Dr Kelvin Picker for his invaluable guidance in all matters HPLC.

References

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

Abstract

Acknowledgments

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