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Radionuclide Imaging of Miniaturized Chemical Analysis Systems
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Analytical Chemistry.
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2004 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 76, no 23, 7102-7108 p.Article in journal (Refereed) Published
Abstract [en]

We propose radionuclide imaging as a valuable tool for the study of molecular interactions in miniaturized systems for chemical analysis. Sensitive and quantitative imaging can be performed with compounds labeled with short-lived positron-emitting radionuclides, such as C-11 and Ga-68, within selected parts of the system. Radionuclide imaging is not restricted to transparent materials since the relatively energetic positrons can penetrate high optical density materials. Experimentally, a radiotracer is introduced into the object of study, which is subsequently placed on a phosphor storage plate. After exposure, the plate is scanned with a laser and a digital, quantitative image can be reconstituted. To demonstrate the concept, three types of microstructures suited for integration in chemical analysis systems were imaged with C-11- and Ga-68-labeled tracers. The influence of factors such as geometry of the object and type of radionuclide on resolution and sensitivity was investigated. The resolution ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol or 2.4-110 pM tracer. The imaging approach was applied to study analyte concentration and sample dilution effects on the performance of a capillary extraction column integrated in an automated LC-ESI-MS system. The utility of the technique was further illustrated by imaging of microchannels in a zeonor plastic compact disk and in a poly(dimethylsiloxane) material for the study of nonspecific peptide adsorption.

Place, publisher, year, edition, pages
2004. Vol. 76, no 23, 7102-7108 p.
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-92493DOI: 10.1021/ac040070eOAI: oai:DiVA.org:uu-92493DiVA: diva2:165597
Available from: 2005-01-11 Created: 2005-01-11 Last updated: 2012-08-03Bibliographically approved
In thesis
1. Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices: Exploration of Radiotracer Chemistry as an Analytical Tool
Open this publication in new window or tab >>Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices: Exploration of Radiotracer Chemistry as an Analytical Tool
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Liquid chromatography – mass spectrometry (LC-MS) methods were developed for the analysis of positron emission tomography (PET) radiotracers in biological matrices. Additionally, radiotracer chemistry was explored as an analytical tool for supporting LC-MS method development and imaging molecular interactions in miniaturised chemical analysis systems.

Conventional radiodetection methods can offer high sensitivity in the analysis of radiotracers in biological matrices, although with the short half-life of PET tracers, this mass sensitivity decreases rapidly with time. This limits the time frame for analysis, and may compromise the precision and accuracy of the later measurements. Performing LC-MS analysis of the dominant stable isotope form of the tracer removes such time restrictions.

An LC-MS/MS method was developed for determination of the tracer flumazenil in human plasma, with high inter-assay precision (RSD < 7%) and accuracy (95 – 104%). The method was applied in a multiple scan PET study where the plasma concentration spanned from 0.07 to 0.21 nM. The method removed the time restrictions associated with radiodetection methods and thus provided the opportunity of analysing a greater number of samples than would have been possible with radioanalysis.

Furthermore, an LC-MS/MS method was developed that provided an efficient metabolic screening tool of potential PET tracers, whereby the substrates could be collected directly from 11C-labelling batches. This permitted repeated incubation experiments without the need of repeated labelling syntheses. A para-methoxy-benzamide analogue of the radiotracer WAY-100635 was thus identified as a potential tracer with improved metabolic stability. Additionally, a capillary LC-MS method was developed with rapid (0.75 min) and efficient (> 99%) on-line high flow-rate extraction for determination of metabolic stability of PET radiotracers.

Finally, the concept of radionuclide imaging of miniaturised chemical analysis systems was demonstrated with the direct study of interactions within capillary extraction columns and microchannels moulded in a plastic CD and poly(dimethylsiloxane).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 61 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 2
Keyword
Analytical chemistry, liquid chromatography - mass spectrometry, radiotracer chemistry, positron emission tomography, biological samples, radionuclide imaging, Analytisk kemi
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-4727 (URN)91-554-6126-3 (ISBN)
Public defence
2005-02-04, B42, BMC, Uppsala, 10:15
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Supervisors
Available from: 2005-01-11 Created: 2005-01-11Bibliographically approved

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Lavén, MartinVelikyan, IrinaBergström, SaraLångström, Bengt

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