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Application of highly sensitive UPLC-MS to determine biodistribution at tracer doses: validation with the 5-HT1A ligand [(18)F]FPWAY.
- Source :
-
Nuclear medicine and biology [Nucl Med Biol] 2009 May; Vol. 36 (4), pp. 389-93. Date of Electronic Publication: 2009 Mar 26. - Publication Year :
- 2009
-
Abstract
- High-sensitivity and high-resolution LC/MS instrumentation has been applied in positron emission tomography (PET) radiopharmaceutical development to provide quantitative measurement of the mass of radiotracers extracted from tissues of rats. We employed the highly sensitive Waters Q-TOF premier MS coupled with an Acquity UPLC system to demonstrate that LC-MS can generate ex vivo biodistribution data for PET 5-HT(1A) ligand FPWAY without the need to radiolabel. For the biodistribution studies, we injected rats with [(18)F]FPWAY containing various amounts of nonradioactive FPWAY. At the end of the allotted time, the animals were killed and six regions of brain and plasma from each animal were processed for quantitative measurement of parent compound concentration by LC-MS. These data were then converted to the differential uptake ratio DUR (%ID/g*body weight/100) and the brain tissue-specific binding ratio to allow direct comparison with data obtained by gamma counting of the coinjected radioactive [(18)F]FPWAY. The DUR and the brain tissue-specific binding ratio calculated using the LC-MS method were highly correlated to the values obtained by standard radioactivity measurements of [(18)F]FPWAY. In conclusion, there was significant concordance between the LC/MS and radioactivity method in determination of DUR and the specific binding ratio in the rat brain. This concordance indicated that high-sensitivity LC/MS is an indispensable tool in evaluating the quantity of administered chemical in tissue as part of the development of new molecular imaging probes.
- Subjects :
- Animals
Brain cytology
Brain metabolism
Chromatography, High Pressure Liquid
Ligands
Male
Mass Spectrometry
Organ Specificity
Radioactive Tracers
Rats
Rats, Sprague-Dawley
Reference Standards
Sensitivity and Specificity
Tissue Distribution
Piperazines metabolism
Piperazines pharmacokinetics
Pyrimidines metabolism
Pyrimidines pharmacokinetics
Receptor, Serotonin, 5-HT1A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9614
- Volume :
- 36
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nuclear medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 19423006
- Full Text :
- https://doi.org/10.1016/j.nucmedbio.2009.01.002