ArticleEJNMMI radiopharmacy and chemistry2024
DESI-TQ-MS imaging for ex vivo brain biodistribution assessment: evaluation of LBT-999, a ligand of the dopamine transporter (DAT).
Article in EJNMMI radiopharmacy and chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Advancements in Ambient Ionisation Mass Spectrometry in 2024: An Annual Review.Analytical science advances · 2025Review
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15 authors.
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Abstract
backgroundSelection of the most promising radiotracer candidates for radiolabeling is a difficult step in the development of radiotracer pharmaceuticals, especially for the brain. Mass spectrometry (MS) is an alternative to study ex vivo the characteristics of candidates, but most MS studies are complicated by the pharmacologic doses injected and the dissection of regions to study candidate biodistribution. In this study, we tested the ability of a triple quadrupole analyzer (TQ LC-MS/MS) to quantify low concentrations of a validated precursor of a radiotracer targeting the DAT (LBT-999) in dissected regions. We also investigated its biodistribution on brain slices using MS imaging with desorption electrospray ionization (DESI) coupled to time-of-flight (TOF) vs. TQ mass analyzers.
resultsTQ LC-MS/MS enabled quantification of LBT-999 injected at sub-tracer doses in dissected striata. DESI-MS imaging (DESI-MSI) with both analyzers provided images of LBT-999 biodistribution on sagittal slices that were consistent with positron emission tomography (PET). However, the TOF analyzer only obtained biodistribution images at a high injected dose of LBT-999, while the TQ analyzer provided biodistribution images at lower injected doses of LBT-999 with a better signal-to-noise ratio. It also allowed simultaneous visualization of endogenous metabolites such as dopamine.
conclusionsOur results show that LC-TQ MS/MS in combination with DESI-MSI can provide important information (biodistribution, specific and selective binding) that can facilitate the selection of the most promising candidates for radiolabeling and support the development of radiotracers.
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