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Fluorine-18 fluoro-2-deoxy-D-glucose (FDG) uptake in brown adipose tissue (BAT) may generate FDG-PET scan misinterpretation. Recent studies have shown reduced FDG uptake in BAT in rats treated with high doses of the beta-blocker propranolol. The aim of this observational study was to present a cohort of patients with high FDG uptake in BAT who underwent a second scan after receiving a low dose of propranolol, to determine whether the use of this premedication could improve the diagnostic confidence of FDG-PET scans by inhibition FDG uptake in BAT, and also whether administration of this drug affects tracer uptake in tumors.Twenty-six cancer patients, presenting with increased BAT FDG uptake, were selected prospectively. On a different day, patients were given propranolol 20 mg orally 60 minutes prior to FDG administration 185–277.5 MBq (5–7.5 mCi) and were scanned again. Basal and postpropranolol BAT SUVmax, and tumor SUVmax (when present) were measured.Mean basal BAT SUVmax was 5.52 ± 2.3. Mean postpropranolol SUVmax was 1.39 ± 0.42 (P < 0.0001). In 11 patients, the basal mean tumor SUVmax was 8.07 ± 6.4, and 7.88 ± 5.9 in postpropranolol scans (P = 0.53). Nine patients showed mediastinal FDG uptake in the basal scan, affecting image interpretation. This was not observed in postpropranolol scans. No adverse effects due to propranolol were encountered.In this patient cohort, there was significant reduction of FDG uptake in BAT following propranolol administration, allowing for adequate interpretation of FDG-PET and software-fused FDG-PET with CT images, particularly in the mediastinal area, without affecting tumor tracer uptake.