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.

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.

• 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
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 40 Issue 8 Pg. 1035-42 (Nov 2013) ISSN: 1872-9614 [Electronic] United States
• PMID: 23969084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Fluorine Radioisotopes
• Liposomes
• Proliferating Cell Nuclear Antigen
• Arabinofuranosyluracil
• Vinblastine
• clevudine
• Vinorelbine

Topics

• Animals
• Arabinofuranosyluracil (analogs & derivatives, metabolism, pharmacokinetics)
• Biological Transport
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Female
• Fluorine Radioisotopes
• Humans
• Liposomes
• Mice
• Positron-Emission Tomography
• Proliferating Cell Nuclear Antigen (metabolism)
• Sarcoma (diagnostic imaging, drug therapy, metabolism, pathology)
• Tomography, Emission-Computed, Single-Photon
• Treatment Outcome
• Vinblastine (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
• Vinorelbine
• Xenograft Model Antitumor Assays