Dataset Information

Response Monitoring with [¹⁸F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

ABSTRACT:

Purpose

The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[¹⁸F]fluorothymidine ([¹⁸F]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 [¹⁸F]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, [¹⁸F]FLT SUV_mean and SUV_max were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUV_max 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 [¹⁸F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADC_mean) did not change in 5-FU-treated rats compared to untreated rats.

Conclusion

This study suggests that 5-FU treatment induces a flare in [¹⁸F]FLT uptake of responsive CC531 tumors in the liver, while the ADC_mean did not change significantly. Future studies in larger groups are warranted to further investigate whether [¹⁸F]FLT PET can discriminate between disease progression and treatment response.

SUBMITTER: Heskamp S

PROVIDER: S-EPMC5498638 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Response Monitoring with [<sup>18</sup>F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

Heskamp Sandra S Heijmen Linda L Gerrits Danny D Molkenboer-Kuenen Janneke D M JDM Ter Voert Edwin G W EGW Heinzmann Kathrin K Honess Davina J DJ Smith Donna-Michelle DM Griffiths John R JR Doblas Sabrina S Sinkus Ralph R Laverman Peter P Oyen Wim J G WJG Heerschap Arend A Boerman Otto C OC

Molecular imaging and biology 20170801 4

<h4>Purpose</h4>The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[<sup>18</sup>F]fluorothymidine ([<sup>18</sup>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.<h4>Procedures</h4>Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals) ...[more]

PMID: 27798786

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