<h3>Purpose/Objective(s)</h3> The goal of this study is to investigate the utility of hybrid <sup>18</sup>FDG PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month and one-year post radiation therapy (RT) in patients with left-sided breast cancer. <h3>Materials/Methods</h3> Fifteen left-sided breast cancer patients are currently enrolled in the RICT-BREAST study (NCT03748030). Serial imaging with hybrid <sup>18</sup>FDG PET/MRI and blood work was obtained at baseline (before RT), at one-month post RT, and at one-year post RT. The hybrid <sup>18</sup>FDG PET/MR imaging protocol consisted of a sixty-minute list-mode <sup>18</sup>FDG PET scan with prior glucose suppression. Myocardial inflammation was quantified by calculating the change of mean <sup>18</sup>FDG standard uptake (meanSUV<sub>bw</sub>) at 40-60 minutes post injection and was grouped based on the supplied artery (left anterior descending (LAD), left circumflex (LC) or right coronary artery (RCA)). MRI assessments, including left ventricle (LV) functional and extracellular volume matrices (ECV), were extracted from T1 (pre and during-constant infusion of gadolinium) and cine images, respectively, and acquired simultaneously during PET acquisition. Cardiac disease and inflammation biomarker measurements of high-sensitivity troponin T (hs-TnT), C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were compared at each timepoint. <h3>Results</h3> Eleven patients received deep-inspiration breath-hold RT (DIBH-RT), while four patients received free-breathing RT (FB-RT), where 4D-CT simulation was performed to define cardiac motion encompassment. To date, all patients have received hybrid <sup>18</sup>FDG PET/MRI cardiac imaging and bloodwork at baseline and at one month after RT. Two patients have received their one-year follow-up <sup>18</sup>FDG PET/MRI scan and bloodwork. At 1-month follow-up, a significant increase (10%) of <sup>18</sup>FDG/PET myocardial uptake (meanSUV<sub>bw</sub>) was detected at LAD territories (p = 0.04). A significant increase in mean ECV, measured with T1-mapping, was observed in slices of the apex (6%) and base (5%) were also detected (p < 0.02). A significant reduction of mean LV stroke volume (-7%) was also identified (p < 0.02). Insignificant changes of all blood work measurements at 1-month follow-up were reported. There was no detectable difference in any cardiac measure between patients who received DIBH-RT and FB-RT. For the two patients who had their one-year follow-ups, an increase in hs-CRP and ESR levels were detected compared to baseline, whereas global reduction of FDG uptake was seen. One patient had an increase of hs-TnT (up to 19ng/L) with left ventricle remodeling reported in echocardiography and a global increase of ECV. <h3>Conclusion</h3> <sup>18</sup>FDG/PET myocardial uptake and functional MR, including SV and ECV were sensitive to changes at 1-month after breast cancer RT with findings suggesting an acute inflammatory response in the heart. One-year median follow-up imaging and bloodwork has been acquired for 2 of 15 patients thus far.