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

作者：Chan Pei Chia; Wu Chun Yi; Chang Wei Ting; Lin Chih Yuan; Tseng Yun Long; Liu Ren Shyan; Alauddin Mian M; Lin Wuu Jyh; Wang Hsin Ell^*

来源：Nuclear Medicine and Biology, 2013, 40(8): 1035-1042.

DOI：10.1016/j.nucmedbio.2013.07.003

• Tumor
• Lipo-VNB
• Therapeutic efficacy
• PET
• [F-18]FMAU

Objective: Previous studies have shown that the accumulation level of FMAU in tumor is proportional to its proliferation rate. This study demonstrated that 2%26apos;-deoxy-2%26apos;-[F-18]fluoro-beta-D-arabinofuranosyluracil ([F-18] 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. %26lt;br%26gt;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 (5 mg/kg) was intravenously administered on days 0, 3 and 6. To monitor the therapeutic efficacy of lipo-VNB, [F-18]FMAU PET was employed to evaluate the proliferation rate of tumor, and it was compared with that observed from [F-18]FDG/[F-18]fluoroacetate PET. The expression of proliferating cell nuclear antigen (PCNA) in tumor during treatment was determined by semiquantitative analysis of immunohistochemical staining. %26lt;br%26gt;Results: A significant inhibition (p %26lt;0.001) in tumor growth was observed on day 3 after a single dose treatment. The tumor-to-muscle ratio (TIM) derived from [18FWMAU-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 [F-18]FDG and [F-18]fluoroacetate microPET imaging did not show significant difference in TIM between the therapeutic and the control groups throughout the entire experimental period. %26lt;br%26gt;Conclusion: Lipo-VNB can effectively impede the growth of NG4TL4 sarcoma. [F-18]FMAU PET is an appropriate modality for early monitoring of the tumor response during the treatment course of lipo-VNB.

• 出版日期2013-11