Biomaterial Database

A novel monoacylglycerol lipase-targeted 18F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network. 2022

Ran Cheng, and Masayuki Fujinaga, and Jing Yang, and Jian Rong, and Ahmed Haider, and Daisuke Ogasawara, and Richard S Van, and Tuo Shao, and Zhen Chen, and Xiaofei Zhang, and Erick R Calderon Leon, and Yiding Zhang, and Wakana Mori, and Katsushi Kumata, and Tomoteru Yamasaki, and Lin Xie, and Shaofa Sun, and Lu Wang, and Chongzhao Ran, and Yihan Shao, and Benjamin Cravatt, and Lee Josephson, and Ming-Rong Zhang, and Steven H Liang

Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.

Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [18F]FEPAD. Pharmacokinetics and binding studies on [18F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [18F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D008994	Monoacylglycerol Lipases	An enzyme that catalyzes the hydrolysis of glycerol monoesters of long-chain fatty acids EC 3.1.1.23.	Glycerol Monoester Hydrolase,Glycerol Monoester Hydrolases,Monoacylglycerol Lipase,Monoglyceride Esterase,Monoglyceride Esterases,Monoglyceride Lipase,Monoglyceride Lipases,Monoglyceride Hydrolase,Esterase, Monoglyceride,Esterases, Monoglyceride,Hydrolase, Glycerol Monoester,Hydrolase, Monoglyceride,Hydrolases, Glycerol Monoester,Lipase, Monoacylglycerol,Lipase, Monoglyceride,Lipases, Monoacylglycerol,Lipases, Monoglyceride,Monoester Hydrolase, Glycerol,Monoester Hydrolases, Glycerol
D002001	Adipose Tissue, Brown	A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids.	Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D049268	Positron-Emission Tomography	An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.	PET Imaging,PET Scan,Positron-Emission Tomography Imaging,Tomography, Positron-Emission,Imaging, PET,Imaging, Positron-Emission Tomography,PET Imagings,PET Scans,Positron Emission Tomography,Positron Emission Tomography Imaging,Positron-Emission Tomography Imagings,Scan, PET,Tomography Imaging, Positron-Emission,Tomography, Positron Emission
D063388	Endocannabinoids	Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.	Endocannabinoid