18F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography

Feng Hu, Patrick J. Morris, Jordi Bonaventura, Hong Fan, William B. Mathews, Daniel P. Holt, Sherry Lam, Matthew Boehm, Robert F. Dannals, Martin G. Pomper, Michael Michaelides, Andrew G. Horti

Research output: Contribution to journalArticlepeer-review


Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a preclinical chemogenetic approach with clinical potential for various disorders. In vivo visualization of DREADDs has been achieved with positron emission tomography (PET) using 11C radiotracers. The objective of this study was to develop DREADD radiotracers labeled with 18F for a longer isotope half-life. A series of non-radioactive fluorinated analogs of clozapine with a wide range of in vitro binding affinities for the hM3Dq and hM4Di DREADD receptors has been synthesized for PET. Compound [18F]7b was radiolabeled via a modified 18F-deoxyfluorination protocol with a commercial ruthenium reagent. [18F]7b demonstrated encouraging PET imaging properties in a DREADD hM3Dq transgenic mouse model, whereas the radiotracer uptake in the wild type mouse brain was low. [18F]7b is a promising long-lived alternative to the DREADD radiotracers [11C]clozapine ([11C]CLZ) and [11C]deschloroclozapine ([11C]DCZ).

Original languageEnglish (US)
Article number113047
JournalEuropean Journal of Medicinal Chemistry
StatePublished - Mar 5 2021


  • Chemogenetics
  • F
  • PET
  • SAR
  • hM3Dq
  • hM4Di

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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