Response Monitoring with [F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

PURPOSE

The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[F]fluorothymidine ([F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.

PROCEDURES

Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.

RESULTS

5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [F]FLT SUV and SUV were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUV at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADC) did not change in 5-FU-treated rats compared to untreated rats.

CONCLUSION

This study suggests that 5-FU treatment induces a flare in [F]FLT uptake of responsive CC531 tumors in the liver, while the ADC did not change significantly. Future studies in larger groups are warranted to further investigate whether [F]FLT PET can discriminate between disease progression and treatment response.