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Purpose: The aim of this study was to evaluate the clinical value of rectal gas distension F-18 FDG PET/CT imaging for the differentiation of the rectal focal uptake lesions. Materials and Methods: Twenty four patients (M:F=11:13, Age 62.8±12.4 years) underwent rectal gas distension F-18 FDG PET/CT, prospectively: initial image at 50-60 min after the intravenous injection of F-18 FDG and rectal distension image after the infusion of air through the anus. Focally increased uptake lesions on initial images but disappeared on rectal distension images defined a physiological uptake. For the differential evaluation of persistent focal uptake lesions on rectal distension images, colonoscopy and histopathologic examination were performed. Results: Among the 24 patients, 27 lesions of focal rectal uptake were detected on initial images of F-18 FDG PET/CT. Of these, 7 lesions were able to judge with physiological uptake because the focal increased uptake disappeared from rectal distension image. Remaining 3 lesions were non-rectal lesions (2 lesions: rectovesical space, 1 lesion: uterine myoma). Among 17 lesions which was showed persistent increased uptake in rectal distension image, 15 lesions were confirmed as the malignant tumor (SUVmax=15.9±6.8) and 2 lesions were confirmed as the benign lesions including adenoma and inflammatory disease. Conclusion: The rectal distension F-18 FDG PET/CT imaging could be an important noninvasive method for the differentiation of malignant and benign focal rectal uptake lesions including physiologic uptake.