Synthesis and imaging validation of [18F]MDL100907 enabled by Ni-mediated fluorination

Hong Ren, Hsiao Ying Wey, Martin Strebl, Ramesh Neelamegam, Tobias Ritter, Jacob M. Hooker

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Several voids exist in reliable positron emission tomography (PET) radioligands for quantification of the serotonin (5HT) receptor system. Even in cases where 5HT radiotracers exist, challenges remain that have limited the utility of 5HT imaging in clinical research. Herein we address an unmet need in 5HT2a imaging using innovative chemistry. We report a scalable and robust synthesis of [18F]MDL100907, which was enabled by a Ni-mediated oxidative fluorination using [18F]fluoride. This first demonstration of a Ni-mediated fluorination used for PET imaging required development of a new reaction strategy that ultimately provided high specific activity [18F]MDL100907. Using the new synthetic strategy and optimized procedure, [18F]MDL100907 was evaluated against [ 11C]MDL100907 for reliability to quantify 5HT2a in the nonhuman primate brain and was found to be superior based on a single scan analysis using the same nonhuman primate. The use of this new 5HT2a radiotracer will afford clinical neuroscience research the ability to distinguish 5HT2a receptor abnormalities binding between healthy subjects and patients even when group differences are small.

Original languageEnglish (US)
Pages (from-to)611-615
Number of pages5
JournalACS Chemical Neuroscience
Volume5
Issue number7
DOIs
StatePublished - Jul 16 2014
Externally publishedYes

Keywords

  • MDL100907
  • PET imaging
  • nickel-mediated
  • serotonin receptors

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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