High-potency ligands for DREADD imaging and activation in rodents and monkeys

Jordi Bonaventura; Mark A.G. Eldridge; Feng Hu; Juan L. Gomez; Marta Sanchez-Soto; Ara M. Abramyan; Sherry Lam; Matthew A. Boehm; Christina Ruiz; Mitchell R. Farrell; Andrea Moreno; Islam Mustafa Galal Faress; Niels Andersen; John Y. Lin; Ruin Moaddel; Patrick J. Morris; Lei Shi; David R. Sibley; Stephen V. Mahler; Sadegh Nabavi; Martin G. Pomper; Antonello Bonci; Andrew G. Horti; Barry J. Richmond; Michael Michaelides

doi:10.1038/s41467-019-12236-z

High-potency ligands for DREADD imaging and activation in rodents and monkeys

Jordi Bonaventura, Mark A.G. Eldridge, Feng Hu, Juan L. Gomez, Marta Sanchez-Soto, Ara M. Abramyan, Sherry Lam, Matthew A. Boehm, Christina Ruiz, Mitchell R. Farrell, Andrea Moreno, Islam Mustafa Galal Faress, Niels Andersen, John Y. Lin, Ruin Moaddel, Patrick J. Morris, Lei Shi, David R. Sibley, Stephen V. Mahler, Sadegh NabaviMartin G. Pomper, Antonello Bonci, Andrew G. Horti, Barry J. Richmond, Michael Michaelides^*

^*Corresponding author for this work

Department of Molecular Biology and Genetics - Neurobiology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

112 Citations (Scopus)

Abstract

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.

Original language	English
Article number	4627
Journal	Nature Communications
Volume	10
Issue	1
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-12236-z
Publication status	Published - 1 Dec 2019

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Bonaventura, J., Eldridge, M. A. G., Hu, F., Gomez, J. L., Sanchez-Soto, M., Abramyan, A. M., Lam, S., Boehm, M. A., Ruiz, C., Farrell, M. R., Moreno, A., Galal Faress, I. M., Andersen, N., Lin, J. Y., Moaddel, R., Morris, P. J., Shi, L., Sibley, D. R., Mahler, S. V., ... Michaelides, M. (2019). High-potency ligands for DREADD imaging and activation in rodents and monkeys. Nature Communications, 10(1), Article 4627. https://doi.org/10.1038/s41467-019-12236-z

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title = "High-potency ligands for DREADD imaging and activation in rodents and monkeys",

abstract = "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.",

author = "Jordi Bonaventura and Eldridge, {Mark A.G.} and Feng Hu and Gomez, {Juan L.} and Marta Sanchez-Soto and Abramyan, {Ara M.} and Sherry Lam and Boehm, {Matthew A.} and Christina Ruiz and Farrell, {Mitchell R.} and Andrea Moreno and {Galal Faress}, {Islam Mustafa} and Niels Andersen and Lin, {John Y.} and Ruin Moaddel and Morris, {Patrick J.} and Lei Shi and Sibley, {David R.} and Mahler, {Stephen V.} and Sadegh Nabavi and Pomper, {Martin G.} and Antonello Bonci and Horti, {Andrew G.} and Richmond, {Barry J.} and Michael Michaelides",

year = "2019",

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doi = "10.1038/s41467-019-12236-z",

language = "English",

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Bonaventura, J, Eldridge, MAG, Hu, F, Gomez, JL, Sanchez-Soto, M, Abramyan, AM, Lam, S, Boehm, MA, Ruiz, C, Farrell, MR, Moreno, A , Galal Faress, IM, Andersen, N, Lin, JY, Moaddel, R, Morris, PJ, Shi, L, Sibley, DR, Mahler, SV, Nabavi, S, Pomper, MG, Bonci, A, Horti, AG, Richmond, BJ & Michaelides, M 2019, 'High-potency ligands for DREADD imaging and activation in rodents and monkeys', Nature Communications, vol. 10, no. 1, 4627. https://doi.org/10.1038/s41467-019-12236-z

TY - JOUR

T1 - High-potency ligands for DREADD imaging and activation in rodents and monkeys

AU - Bonaventura, Jordi

AU - Eldridge, Mark A.G.

AU - Hu, Feng

AU - Gomez, Juan L.

AU - Sanchez-Soto, Marta

AU - Abramyan, Ara M.

AU - Lam, Sherry

AU - Boehm, Matthew A.

AU - Ruiz, Christina

AU - Farrell, Mitchell R.

AU - Moreno, Andrea

AU - Galal Faress, Islam Mustafa

AU - Andersen, Niels

AU - Lin, John Y.

AU - Moaddel, Ruin

AU - Morris, Patrick J.

AU - Shi, Lei

AU - Sibley, David R.

AU - Mahler, Stephen V.

AU - Nabavi, Sadegh

AU - Pomper, Martin G.

AU - Bonci, Antonello

AU - Horti, Andrew G.

AU - Richmond, Barry J.

AU - Michaelides, Michael

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-019-12236-z

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AN - SCOPUS:85073152110

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

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ER -

High-potency ligands for DREADD imaging and activation in rodents and monkeys

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