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Although 3&#8242;-deoxy-3&#8242;[(18)F]-fluorothymidine (FLT)-positron emission tomography (PET) has been utilized for tumor response assessment to neoadjuvant chemotherapy in soft tissue sarcomas, it has not been exploited for the assessment of early response to systematically targeted therapies. Herein, we investigated the ¹⁸F-FLT PET/CT kinetics in patients with sarcoma who received targeted therapies. Among 15 patients with sarcoma who underwent ¹⁸F-FLT PET/CT, 5 patients (33%) patients were imaged at three time points: At baseline and at 1&#8722;15 weeks (<i>MDM2</i>-inhibitor treatment), and 10 patients (67%) were imaged twice: At baseline and at 1&#8722;4 weeks (<i>MDM2 inhibitor</i>, <i>n</i> = 5; <i>c-met</i> inhibitor <i>n</i> = 5). The patients with sarcoma had a total of 18 identifiable tumors. Twelve of 15 patients (80%) demonstrated ¹⁸F-FLT concentrations changes early, i.e., at 1&#8722;4 weeks. Eight patients responded (53.3%), four patients progressed (26.7%) based on FLT change of more than 10% increase, and three patients (20%) demonstrated no change. ¹⁸F-FLT PET/CT may be used for early response imaging to molecularly targeted therapies in patients with sarcoma. Further larger studies in specific sarcoma sub-types are warranted.