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SINAPSE experts from around Scotland have developed ten online modules designed to explain medical imaging. They are freely available and are intended for non-specialists.

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Online Short Courses

Radiotracer properties determined by high performance liquid chromatography: a potential tool for brain radiotracer discovery

Author(s): A. A. S. Tavares, J. Lewsey, D. Dewar, S. L. Pimlott

Introduction: Previously, development of novel brain radiotracers has largely relied on simple screening tools. Improved selection methods at the early stages of radiotracer discovery and an increased understanding of the relationships between in vitro physicochemical and in vivo radiotracer properties are needed. We investigated if high performance liquid chromatography (HPLC) methodologies could provide criteria for lead candidate selection by comparing HPLC measurements with radiotracer properties in humans. Methods: Ten molecules, previously used as radiotracers in humans, were analysed to obtain the following measures: partition coefficient (Log P); permeability (P,); percentage of plasma protein binding (%PPB); and membrane partition coefficient (K(m)). Relationships between brain entry measurements (Log P, P %PPB) and in vivo brain percentage injected dose (%ID); and K specific binding in vivo (BP(ND)) were investigated. Log P values obtained using in silico packages and flask methods were compared with Log P values obtained using HPLC. Results: The modelled associations with %ID were stronger for %PPB (r(2)=0.65) and P, (r(2)=0.77) than for Log P (r(2)=0.47) while 86% of BPND variance was explained by K. Log P values were variable dependant on the methodology used. Conclusions: Log P should not be relied upon as a predictor of blood-brain barrier penetration during brain radiotracer discovery. HPLC measurements of permeability, %PPB and membrane interactions may be potentially useful in predicting in vivo performance and hence allow evaluation and ranking of compound libraries for the selection of lead radiotracer candidates at early stages of radiotracer discovery. (C) 2012 Elsevier Inc. All rights reserved.

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ISBN: 0969-8051
Publication Year: 2012
Periodical: Nuclear Medicine and Biology
Periodical Number: 1
Volume: 39
Pages: 127-135
Author Address: Tavares, AAS Univ Glasgow, Wellcome Surg Inst, Garscube Estate, Glasgow G61 1QH, Lanark, Scotland Univ Glasgow, Inst Neurosci & Psychol, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland Univ Glasgow, Inst Hlth & Wellbeing, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland Univ Glasgow, Glasgow G11 6NT, Lanark, Scotland N Glasgow Univ Hosp NHS Trust, Glasgow G11 6NT, Lanark, Scotland