Diagnostic Superiority of Dual-Time Point [(18)F]FDG PET/CT to Differentiate Malignant from Benign Soft Tissue Tumors

[(18)F]FDG PET/CT is used in the workup of indeterminate soft tissue tumors (STTs) but lacks accuracy in the detection of malignant STTs. The aim of this study is to evaluate whether dual-time point [(18)F]FDG PET/CT imaging (DTPI) can be useful in this indication. In this prospective study, [(18)F]FDG PET/CT imaging was performed 1 h (t1) and 3 h (t2) after injection. Tumor uptake (SUVmax) was calculated at each time point to define a retention index (RI) corresponding to the variation between t1 and t2 (%). Sixty-eight patients were included, representing 20 benign and 48 malignant tumors (including 40 sarcomas). The RI was significantly higher in malignant STTs than in benign STTs (median: +21.8% vs. −2%, p < 0.001). An RI of >14.3% predicted STT malignancy with a specificity (Sp) of 90% and a sensitivity (Se) of 69%. An SUVmax(t1) of >4.5 was less accurate with an Sp of 80% and an Se of 60%. In a subgroup of tumors with at least mild [(18)F]FDG uptake (SUVmax ≥ 3; n = 46), the RI significantly outperformed the diagnostic accuracy of SUVmax (AUC: 0.88 vs. 0.68, p = 0.01). DTPI identifies malignant STT tumors with high specificity and outperforms the diagnostic accuracy of standard PET/CT.