Monitoring tumor response with [18F]FMAU in a sarcoma-bearing mouse model after liposomal vinorelbine treatment.

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)F]fluoro-β-d-arabinofuranosyluracil ([(18)F]FMAU) 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 mm(3) (day 0), lipo-VNB (5mg/kg) was intravenously administered on days 0, 3 and 6. To monitor the therapeutic efficacy of lipo-VNB, [(18)F]FMAU PET was employed to evaluate the proliferation rate of tumor, and it was compared with that observed from [(18)F]FDG/[(18)F]fluoroacetate 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)F]FMAU-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)F]FDG and [(18)F]fluoroacetate 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)F]FMAU PET is an appropriate modality for early monitoring of the tumor response during the treatment course of lipo-VNB.