Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 61, Issue 4, Pages 604-607Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.119.231985
Keywords
translocator protein (TSPO); P2X7; neuroinflammation; amyotrophic lateral sclerosis; brain specimen
Funding
- Flanders, Belgium (FWO) [1179620N, 1S46219N]
- ALS Liga Belgie
- KU Leuven funds Een Hart voor ALS
- Laeversfonds voor ALS Onderzoek
- FWO, KU Leuven
- Janssen Pharmaceuticals
- Novartis Pharma AG
- GE Healthcare U.K.
- UCB
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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 F-18-DPA714, a second-generation translocator protein tracer, with C-11-JNJ717, a novel P2X7R tracer, in vitro and in vivo in ALS. Methods: For the in vitro portion of the study, autoradiography with F-18-DPA714 and C-11-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 F-18-DPA714 and C-11-JNJ717. Volume-of-distribution images were calculated using Logan plots and analyzed on a volume-of-interest basis. Results: Autoradiography showed no difference in C-11-JNJ717 binding but did show increased F-18-DPA714 binding in the motor cortex correlating with Iba1 expression (glial cells). Similar findings were observed in vivo, with a 13% increase in F-18-DPA714 binding in the motor cortex. Conclusion: In symptomatic ALS patients, F-18-DPA714 showed increased signal whereas C-11-JNJ717 was not elevated.
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