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Objectives: The aim of this study is to assess the value of the F-choline PET/computed tomography (CT) in predicting significant prostate cancer (sPCa) in patients with persistently increased prostate-specific antigen (PSA) levels and previous negative biopsies. To study the possible predictive added value of F-choline PET/CT to clinical variables and biomarkers derived from PSA in detecting sPCa., Methods: We evaluated patients who underwent F-choline PET/CT because of ongoing suspicion of prostate cancer (PCa) due to elevated PSA levels (4-20 ng/mL) and at least one previous negative or no conclusive prostate biopsy for PCa. Age, PSA, free PSA, free/total PSA ratio, PSA velocity, PSA doubling time, PSA density and score risk were obtained. F-choline PET/CT was classified as negative/positive (PET-categorical). Additionally, we subclassified F-choline PET/CT according to the radiotracer uptake patterns (PET-pattern). The reference standard was the histological confirmation. Accuracy of PET/CT was evaluated. Univariate and multivariate logistic regression analyses were performed for metabolic and clinical variables., Results: A total of 78 patients were included in our study, 23 had PCa (15 with sPCa). The PET pattern showed the highest accuracy and was the most powerful predictor of sPCa. In this research, the prediction of sPCa was improved combining PET pattern and score risk., Conclusion: F-choline PET/CT is a potential tool for predicting sPCa in patients with persistently increased PSA levels and previous negative biopsies, and also it could improve the performance of score risk in predicting sPCa.