Microglia imaging in methamphetamine use disorder: a positron emission tomography study with the 18 kDa translocator protein radioligand [F‐18]FEPPA

• Published in: Addiction biology Vol. 26; no. 1; pp. e12876 - n/a
• Main Authors: Rathitharan, Gausiha, Truong, Jennifer, Tong, Junchao, McCluskey, Tina, Meyer, Jeffrey H., Mizrahi, Romina, Warsh, Jerry, Rusjan, Pablo, Kennedy, James L., Houle, Sylvain, Kish, Stephen J., Boileau, Isabelle
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2021
• Subjects: [F‐18]FEPPA; Addictions; Adult; Amphetamine-Related Disorders - diagnostic imaging; Amphetamine-Related Disorders - metabolism; Anilides - metabolism; Brain - metabolism; Case-Control Studies; Cell activation; Dosage; Female; Fluorine Radioisotopes - metabolism; Humans; Magnetic Resonance Imaging; Male; Methamphetamine; Methamphetamine - metabolism; methamphetamine use disorder; Microglia; Microglia - physiology; Microglial cells; Middle Aged; Neuroimaging; Positron emission tomography; Pyridines - metabolism; Radiopharmaceuticals - metabolism; Receptors, GABA - metabolism; Therapeutic applications; Tomography; translocator protein 18 kDa; [F-18]FEPPA; positron emission tomography; microglia; translocator protein 18 kDa; methamphetamine use disorder
• ISSN: 1355-6215; 1369-1600
• DOI: 10.1111/adb.12876

Activation of brain microglial cells, microgliosis, has been linked to methamphetamine (MA)–seeking behavior, suggesting that microglia could be a new therapeutic target for MA use disorder. Animal data show marked brain microglial activation following acute high‐dose MA, but microglial status in human MA users is uncertain, with one positron emission tomography (PET) investigation reporting massively and globally increased translocator protein 18 kDa (TSPO; [C‐11](R)‐PK11195) binding, a biomarker for microgliosis, in MA users. Our aim was to measure binding of a second‐generation TSPO radioligand, [F‐18]FEPPA, in brain of human chronic MA users. Regional total volume of distribution (VT) of [F‐18]FEPPA was estimated with a two‐tissue compartment model with arterial plasma input function for 10 regions of interest in 11 actively using MA users and 26 controls. A RM‐ANOVA corrected for TSPO rs6971 polymorphism was employed to test significance. There was no main effect of group on [F‐18]FEPPA VT (P = .81). No significant correlations between [F‐18]FEPPA VT and MA use duration, weekly dosage, blood MA concentrations, regional brain volumes, and self‐reported craving were observed. Our preliminary findings, consistent with our earlier postmortem data, do not suggest substantial brain microgliosis in MA use disorder but do not rule out microglia as a therapeutic target in MA addiction. Absence of increased [F‐18]FEPPA TSPO binding might be related to insufficient MA dose or blunting of microglial response following repeated MA exposure, as suggested by some animal data. Animal data show marked brainmicroglial activation following methamphetamine (MA) following acute high dose MA but microglial status inhuman MA users is uncertain. We measured binding of [F‐18]FEPPA to TSPO, a microglial marker, in brainof persons who had MA use disorder. Our finding of normal FEPPA binding does not suggest substantial brainmicrogliosis in MA use disorder, although this does not rule out microglia as a potential therapeutic target inMA addiction.