Abstract 803: Elevated neuroinflammation in women with breast cancer: initial insights from [11C]PBR28 PET/MR imaging

Abstract Introduction: As breast cancer survivorship rises, addressing the long-term side effects of cancer and its treatment is crucial. Chemotherapy has been linked to neuroinflammation, leading to cognitive and neurological impairments. However, other treatments (e.g., surgery, endocrine therapy) or related conditions (e.g., pain, cancer progression) may impact neuroinflammation as well. Methods: This cross-sectional study used Siemens 3T integrated positron emission tomography-magnetic resonance imaging (PET/MRI) with the radioligand [11C]PBR28, which binds to the neuroinflammation marker 18kDa translocator protein (TSPO), to assess the extent and distribution of neuroinflammation in two age-matched cohorts of women with and without breast cancer. A T1-weighted volume (MEMPRAGE; voxel size = 1x1x1mm3) was acquired simultaneously and used for attenuation correction of PET data and spatial normalization to the MNI space. Standardized uptake values ratios (SUVR) were computed from 60-90 min post-[11C]PBR28 injection data, intensity normalized by whole brain signal, spatially smoothed (FWHM=8mm) and normalized to the MNI template. PET imaging data were analyzed and processed using FSL and FreeSurfer. A mixed effects ordinary least squares analysis, using a cluster-forming threshold of z=2.3 and a cluster size threshold of p<0.05 was conducted. Mean PET signal in the regional clusters was determined, and an exploratory comparison in neuroinflammation ([11C]PBR28 signal) made between women with and without breast cancer, who did or did not receive chemotherapy (Mann-Whitney U test). Results: Twelve breast cancer patients (age=63±9) and 6 matched healthy controls (age=57±10) were included in this analysis. Compared to healthy controls, breast cancer patients showed significant increased [11C]PBR28 signal uptake in the middle cingulate cortex and underlying white matter (SUVRBC=0.95±0.03, SUVRHC=0.85±0.04). No significant differences were observed between women with (n=7) and without (n=5) chemotherapy (U=15.00, p=0.685). Conclusions: These preliminary findings indicate increased neuroinflammation in breast cancer patients compared to age-matched controls, independent of chemotherapy. These preliminary findings suggest that cancer or other treatments may contribute to neuroinflammation. Larger studies with focused analysis of region(s) of interest are needed to confirm these results. Citation Format: Yehui Zhu, Natalie Swanson, Mehrbod Mohammadian, Jennifer Murphy, Minhae Kim, Ann Partridge, Marilyn Hammer, Robert Edwards, Kristin Schreiber, Marco Loggia. Elevated neuroinflammation in women with breast cancer: initial insights from [11C]PBR28 PET/MR imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 803.