High-potency ligands for DREADD imaging and activation in rodents and monkeys.
Jordi BonaventuraMark A G EldridgeFeng HuJuan L GomezMarta Sanchez-SotoAra M AbramyanSherry LamMatthew A BoehmChristina RuizMitchell R FarrellAndrea MorenoIslam Mustafa Galal FaressNiels AndersenJohn Y LinRuin MoaddelPatrick J MorrisLei ShiDavid R SibleyStephen V MahlerSadegh NabaviMartin G PomperAntonello BonciAndrew G HortiBarry J RichmondMichael MichaelidesPublished in: Nature communications (2019)
Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for human applications as well. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine, making it difficult to apply in basic and translational applications. Here we report the development of two novel DREADD agonists, JHU37152 and JHU37160, and the first dedicated 18F positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. We show that JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons, and at their long-range projections, enabling noninvasive and longitudinal neuronal projection mapping.
Keyphrases
- positron emission tomography
- computed tomography
- pet imaging
- pet ct
- high resolution
- cerebral ischemia
- endothelial cells
- cross sectional
- spinal cord
- magnetic resonance imaging
- image quality
- magnetic resonance
- climate change
- cancer therapy
- brain injury
- induced pluripotent stem cells
- pluripotent stem cells
- resting state
- subarachnoid hemorrhage
- dual energy
- real time pcr
- high density