title: Monitoring tumor response with [18F]FMAU in a sarcoma-bearing mouse model after liposomal vinorelbine treatment.
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)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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors: Pei-Chia
authors: PC
authors: Chan
authors: Chun-Yi
authors: CY
authors: Wu
authors: Wei-Ting
authors: WT
authors: Chang
authors: Chih-Yuan
authors: CY
authors: Lin
authors: Yun-Long
authors: YL
authors: Tseng
authors: Ren-Shyan
authors: RS
authors: Liu
authors: Mian M
authors: MM
authors: Alauddin
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Hsin-Ell
authors: HE
authors: Wang
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008081:Liposomes; D051379:Mice; D049268:Positron-Emission Tomography; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012509:Sarcoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays
chemical_list: D005462:Fluorine Radioisotopes; D008081:Liposomes; D018809:Proliferating Cell Nuclear Antigen; D001086:Arabinofuranosyluracil; D014747:Vinblastine; C034935:clevudine; D000077235:Vinorelbine
keywords: Lipo-VNB; PET; Therapeutic efficacy; Tumor; [(18)F]FMAU