Abstract Objective Previous studies have shown that the accumulation level of FMAU in tumor is proportional to its proliferation rate. This study demonstrated that 2′-deoxy-2′-18 Ffluoro-β- d -arabinofuranosyluracil (18 FFMAU) is a promising PET probe for noninvasively monitoring the therapeutic efficacy of 6% PEGylated liposomal vinorelbine (lipo-VNB) in a subcutaneous murine NG4TL4 sarcoma mouse model. Methods Female syngenic FVB/N mice were inoculated with NG4TL4 cells in the right flank. After tumor size reached 150 ± 50 mm3 (day 0), lipo-VNB (5 mg/kg) was intravenously administered on days 0, 3 and 6. To monitor the therapeutic efficacy of lipo-VNB, 18 FFMAU PET was employed to evaluate the proliferation rate of tumor, and it was compared with that observed from 18 FFDG/18 Ffluoroacetate PET. The expression of proliferating cell nuclear antigen (PCNA) in tumor during treatment was determined by semiquantitative analysis of immunohistochemical staining. Results A significant inhibition (p < 0.001) in tumor growth was observed on day 3 after a single dose treatment. The tumor-to-muscle ratio ( T/M ) derived from 18 FFMAU-PET images of lipo-VNB-treated group declined from 2.33 ± 0.16 to 1.26 ± 0.03 after three doses of treatment, while that of the control remained steady. The retarded proliferation rate of lipo-VNB-treated sarcoma was confirmed by PCNA immunohistochemistry staining. However, both 18 FFDG and 18 Ffluoroacetate microPET imaging did not show significant difference in T/M between the therapeutic and the control groups throughout the entire experimental period. Conclusion Lipo-VNB can effectively impede the growth of NG4TL4 sarcoma. 18 FFMAU PET is an appropriate modality for early monitoring of the tumor response during the treatment course of lipo-VNB.