Rapid analysis for metabolites of 11C-labelled drugs: fate of [11C]-S-4-(tert.-butylamino-2-hydroxypropoxy)-benzimidazol-2-one in the dog

Journal of Chromatography
H A JonesG W Taylor

Abstract

Positron emission tomography (PET) requires the use of compounds labelled with short-lived, positron-emitting isotopes (e.g., t1/2 of 11C approximately 120 min). As the concentration of unbound, non-metabolised drug is required as the input function for modeling, this presents particular problems for the study of the kinetics and metabolism of such compounds. We have now developed a rapid extraction procedure, followed by high-performance liquid chromatography using a short analytical column coupled to an on-line gamma-detector to determine the metabolism and kinetics of a non-selective beta-adrenergic antagonist of high affinity, S-4-(tert.-butylamino-2-hydroxypropoxy)benzimidazol-2-one. This antagonist is potentially well suited to the non-invasive localisation of beta-receptors in vivo. The ligand was rapidly taken up into the beta-receptor pool or excreted in urine, with less than 5% of the drug converted to metabolites. Plasma protein binding was only 16%. No significant metabolism of the ligand was observed in the anaesthetised dog, and, therefore, no correction for blood metabolite concentration is required for kinetic analysis of the 11C-labelled ligand during PET studies in this species. The analytical method reported ...Continue Reading

References

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Citations

Jan 20, 1995·Journal of Chromatography. B, Biomedical Applications·A van WaardeW Vaalburg
Dec 31, 2003·Nuclear Medicine and Biology·Jeanne M LinkJames H Caldwell
May 17, 2000·Pharmaceutica acta Helvetiae·V W PikeP G Camici
Mar 10, 2016·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Gwen M BernackiJohn R Stratton
Jan 18, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·James H CaldwellJohn R Stratton

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