Imaging Monoacylglycerol Lipase A First-in-Human Positron Emission Tomography Study with [18F]MAGL-2102
Year: 2026
Type: preprint
Abstract: Background Monoacylglycerol lipase (MAGL) has emerged over the past decade as a promising target for multiple clinical indications with therapeutics currently under investigation in phase I and II clinical trials. Quantification of MAGL in vivo using positron emission tomography (PET) imaging is therefore essential for elucidating its role in disease and facilitating the development of cannabinoid-targeted therapies. This study presents the first-in-human evaluation of a novel reversible PET radiotracer, [ 18 F]MAGL-2102. Results. Six healthy participants (mean age: 27.5 ± 10.7, 3 males, 3 female) underwent dynamic PET brain scans following administration of [ 18 F]MAGL-2102 (178.11 ± 17.04 MBq), with arterial blood sampling. Brain PET analysis demonstrated low brain uptake, with standardized uptake values ranging from 0.66 to 0.81 in cortical regions and a mean Logan distribution volume ( V T ) value of 0.13 mL/cm 3 . Plasma analysis indicated a parent fraction of approximately 88 ± 4.4% by the end of the scan and a plasma-free fraction of 0.67% ± 0.03%. In addition, whole-body dynamic PET scans (181.63 ± 4.15 MBq) were performed in two participants (1 male, 1 female) for dosimetry analysis. The total effective dose was 2.08 mSv for the male and 3.10 mSv for the female. The gallbladder received the highest absorbed dose, while the brain received the lowest. Conclusion. Despite promising observations in rodent and non-human primates, [ 18 F]MAGL-2102 demonstrates low brain uptake and is therefore unlikely to serve as a reliable tool for imaging MAGL in vivo in brain of humans; however, these findings aim to guide future MAGL radioligands discovery for human PET imaging.
Source: Research Square
Institutions: Centre for Addiction and Mental Health, Emory University
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7166800849