Synthesis and preclinical evaluation of [11C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL)

Muneer Ahamed; Bala Attili; Daisy van Veghel; Maarten Ooms; Philippe Berben; Sofie Celen; Michel Koole; Lieven Declercq; Juha R. Savinainen; Jarmo T. Laitinen; Alfons Verbruggen; Guy Bormans

doi:10.1016/j.ejmech.2017.04.066

Synthesis and preclinical evaluation of [¹¹C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL)

Muneer Ahamed, Bala Attili, Daisy van Veghel, Maarten Ooms, Philippe Berben, Sofie Celen, Michel Koole, Lieven Declercq, Juha R. Savinainen, Jarmo T. Laitinen, Alfons Verbruggen, Guy Bormans

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [¹¹C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [¹¹C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [¹¹C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.

Original language	English
Pages (from-to)	104-113
Number of pages	10
Journal	European Journal of Medicinal Chemistry
Volume	136
DOIs	https://doi.org/10.1016/j.ejmech.2017.04.066
Publication status	Published or Issued - 2017
Externally published	Yes

Keywords

Biodistribution
MAGL
MJN110
PET imaging
[C]MA-PB-1

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.ejmech.2017.04.066

Cite this

Ahamed, M., Attili, B., van Veghel, D., Ooms, M., Berben, P., Celen, S., Koole, M., Declercq, L., Savinainen, J. R., Laitinen, J. T., Verbruggen, A., & Bormans, G. (2017). Synthesis and preclinical evaluation of [¹¹C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL). European Journal of Medicinal Chemistry, 136, 104-113. https://doi.org/10.1016/j.ejmech.2017.04.066

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title = "Synthesis and preclinical evaluation of [11C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL)",

abstract = "MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [11C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [11C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [11C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.",

keywords = "Biodistribution, MAGL, MJN110, PET imaging, [C]MA-PB-1",

author = "Muneer Ahamed and Bala Attili and {van Veghel}, Daisy and Maarten Ooms and Philippe Berben and Sofie Celen and Michel Koole and Lieven Declercq and Savinainen, {Juha R.} and Laitinen, {Jarmo T.} and Alfons Verbruggen and Guy Bormans",

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year = "2017",

doi = "10.1016/j.ejmech.2017.04.066",

language = "English",

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Ahamed, M, Attili, B, van Veghel, D, Ooms, M, Berben, P, Celen, S, Koole, M, Declercq, L, Savinainen, JR, Laitinen, JT, Verbruggen, A & Bormans, G 2017, 'Synthesis and preclinical evaluation of [¹¹C]MA-PB-1 for in vivo imaging of brain monoacylglycerol lipase (MAGL)', European Journal of Medicinal Chemistry, vol. 136, pp. 104-113. https://doi.org/10.1016/j.ejmech.2017.04.066

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AU - Ahamed, Muneer

AU - Attili, Bala

AU - van Veghel, Daisy

AU - Ooms, Maarten

AU - Berben, Philippe

AU - Celen, Sofie

AU - Koole, Michel

AU - Declercq, Lieven

AU - Savinainen, Juha R.

AU - Laitinen, Jarmo T.

AU - Verbruggen, Alfons

AU - Bormans, Guy

PY - 2017

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AB - MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [11C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [11C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110. These initial results suggest that [11C]MA-PB-1 is a suitable tracer for in vivo imaging of MAGL.

KW - Biodistribution

KW - MAGL

KW - MJN110

KW - PET imaging

KW - [C]MA-PB-1

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