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 SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5FU (60 mg/kg) and returned to baseline at day 14 (SUVmax 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 uptakewere observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5FU-treated rats compared to untreated rats. Electronic supplementary material The online version of this article (doi:10.1007/s11307-016-1021-2) contains supplementary material, which is available to authorized users. C o r r e s p o n d e n c e t o : S a n d r a H e s k a m p ; e m a i l : [email protected] Conclusion: This study suggests that 5-FU treatment induces a flare in [F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmean 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.