Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.
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Authors
Heskamp, S
Heijmen, L
Gerrits, D
Molkenboer-Kuenen, JDM
Ter Voert, EGW
Heinzmann, K
Honess, DJ
Smith, D-M
Griffiths, JR
Doblas, S
Sinkus, R
Laverman, P
Oyen, WJG
Heerschap, A
Boerman, OC
Heijmen, L
Gerrits, D
Molkenboer-Kuenen, JDM
Ter Voert, EGW
Heinzmann, K
Honess, DJ
Smith, D-M
Griffiths, JR
Doblas, S
Sinkus, R
Laverman, P
Oyen, WJG
Heerschap, A
Boerman, OC
Document Type
Journal Article
Date
2017-08
Date Accepted
2017-07-09
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 SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5-FU (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 [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) 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 ADCmean 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.
Citation
Molecular imaging and biology, 2017, 19 (4), pp. 540 - 549
Source Title
Publisher
ISSN
1536-1632
eISSN
1860-2002
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Research Team
Translational Molecular Imaging