TSPO Versus P2X7 as a Target for Neuroinflammation: An In Vitro and In Vivo Study

Abstract

Neuroinflammation is important in amyotrophic lateral sclerosis (ALS). The P2X7 receptor (P2X7R) is a promising target for neuroinflammation. The objective of this study was to compare ¹⁸F-DPA714, a second-generation translocator protein tracer, with ¹¹C-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with ¹⁸F-DPA714 and ¹¹C-JNJ717 was performed on human ALS brain sections in comparison to immunofluorescence with Iba1 and GFAP. For the in vivo portion, 3 male patients with early-stage ALS (59.3 ± 7.2 y old) and 6 healthy volunteers (48.2 ± 16.5 y old, 2 men and 4 women) underwent dynamic PET/MR scanning with ¹⁸F-DPA714 and ¹¹C-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in ¹¹C-JNJ717 binding but did show increased ¹⁸F-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in ¹⁸F-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, ¹⁸F-DPA714 showed increased signal whereas ¹¹C-JNJ717 was not elevated.