D108-13 Suppressed Neuroinflammatory Activity Following Two Week E-cigarette Exposure in Adolescent Mice Using [18F]feppa Micropet Imaging

Rationale Over the past decade, e-cigarette use (vaping) has become a predominant method of nicotine delivery among young people, reshaping patterns of consumption and exposure among tobacco users. Traditional cigarettes have been shown to decrease a marker for neuroinflammation in the brains of cigarette smokers, but the impact of e-cigarette vaping on neuroinflammation is unknown. The objective of this study was to measure the marker for neuroinflammation in mice via microPET following sub-acute (two weeks) e-cigarette exposure. Based on prior studies that show that traditional cigarette use alters inflammatory signaling and reduces neuroimmune activation, and that nicotine has anti-inflammatory properties, we hypothesized that e-cigarette use will similarly demonstrate decreased neuroinflammatory activation due to the ingredient common between these two inhalants. Methods Twelve female adolescent C57BL/6 mice were randomized into two inhalant groups: air controls and JUUL™ Virginia Tobacco aerosol exposure. Exposures were conducted for 2 hours/day, 5 days/week, for two weeks (whole-body SciREQ InExpose system). After the final exposure, mice received intravenous [18F]FEPPA (97-183uCi) prior to microPET imaging. As described previously (Brody et al 2025), mice were analyzed using Inviscan/Scintica IRIS microPET (see Figure A-F). The radiotracer [18F]FEPPA binds to the translocator protein (TSPO), which is an outer mitochondrial membrane protein that is highly expressed in CNS glial cells, and is a marker of activated immune cells (neuroinflammation). Scans were reconstructed using filtered back-projection (FBP) and standard uptake values (SUVs) were determined to compare inflammatory responses between groups. Results Analysis of all frames in air-control mice (n = 3) yielded an average SUVx1000 of 411.96±187.78; whereas e-cigarette-exposed mice (n = 3) exhibited an average SUVx1000 of 255.23±141.69. When excluding outer frame noise and focusing primarily on the center frames, air control mice demonstrated an average SUVx1000 of 425.07±185.18, compared to 280.75±133.07 in e-cigarette-exposed mice (see Max SUV data in Figure G). Parallel mice (n = 3 per exposure) underwent harvest and storage of brains. Conclusion This data suggests that e-cigarette vaped mice have decreased [18F]FEPPA binding, thus, lower TSPO expression, relative to air controls. This pattern aligns with previous findings that traditional cigarettes decrease inflammatory responses in the brain and supports the hypothesis that nicotine within e-cigarette aerosols suppresses neuroinflammatory responses. Protein and RNA level assessments can be done on brain tissue for more granular detail. In future studies, it may be beneficial to reference computed tomography (CT) scans for deeper characterization of areas of neuroinflammation with more accurate localization of radiotracer uptake.