Monitoring tumor response with [18F]FMAU in a sarcoma-bearing mouse model after liposomal vinorelbine treatment |
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| Authors: | Pei-Chia Chan Chun-Yi Wu Wei-Ting Chang Chih-Yuan Lin Yun-Long Tseng Ren-Shyan Liu Mian M Alauddin Wuu-Jyh Lin Hsin-Ell Wang |
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| Institution: | 1. Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan;2. Taiwan Liposome Company, Taipei, Taiwan;3. Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;4. Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan;5. Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan;6. Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, USA;7. Institute of Nuclear Energy Research, Atomic Energy Council, Tao-Yuan City, Taiwan;8. Biophotonics & Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan |
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| Abstract: | ObjectivePrevious studies have shown that the accumulation level of FMAU in tumor is proportional to its proliferation rate. This study demonstrated that 2′-deoxy-2′-18F]fluoro-β-d-arabinofuranosyluracil (18F]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.MethodsFemale 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, 18F]FMAU PET was employed to evaluate the proliferation rate of tumor, and it was compared with that observed from 18F]FDG/18F]fluoroacetate PET. The expression of proliferating cell nuclear antigen (PCNA) in tumor during treatment was determined by semiquantitative analysis of immunohistochemical staining.ResultsA 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 18F]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 18F]FDG and 18F]fluoroacetate microPET imaging did not show significant difference in T/M between the therapeutic and the control groups throughout the entire experimental period.ConclusionLipo-VNB can effectively impede the growth of NG4TL4 sarcoma. 18F]FMAU PET is an appropriate modality for early monitoring of the tumor response during the treatment course of lipo-VNB. |
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