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J Nucl Med. 2008; 49 (Supplement 1):328P
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Oncology-Basic Science: Therapy, Metrics & Intervention

Therapy, Metrics & Intervention Posters

[18F]Fluorocholine PET and MRI imaging of transgenic hepatocellular carcinoma mouse model response to FGF19 targeted therapy

Jan Marik1, Leanne McFarland1, Tom Le1, Kathy Hotzel2, Dorothy French2, Joan Greve1 and Simon Williams1

1 Biomedical Imaging; 2 Pathology, Genentech Inc., South San Francisco, California

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Objectives: Early detection and subsequent therapy monitoring of hepatocellular carcinoma (HCC) are crucial for successful treatment and patient survival. Current standard imaging protocols for HCC diagnosis and monitoring consist of CT and MRI. PET imaging using FDG provided 50-70% sensitivity for HCC detection while [18F]fluorocholine (FCH) has been shown to detect early lesions with 100% sensitivity compared to CT and MRI. We have shown that fibroblast growth factor 19 (FGF19) and its cognate receptor FGFR4 are coexpressed in primary human liver, lung and colon tumors. The ectopic expression of FGF19 in mice promotes HCC and the blocking of its interaction with FGFR4 using a specific antibody (1A6) slows tumor progression. In this paper, we report the evaluation of FCH PET and MRI to monitor the progress of liver lesions in a transgenic mouse model treated with 1A6.

Methods: Tumor burden was calculated as 100x[total tumor volume]/[total liver volume].

Results: FCH PET provided tumor to background uptake ratio 1.6. The initial tumor burden determined at week 0 by MRI and FCH PET was 6.5% and 8.5%, respectively. At week 2, the tumor burden for treated animals decreased to 3.8% as determined by FCH PET and 4.9% by MRI. The non-treated group showed tumor growth to 16.5% (PET) and 16.9% (MRI). At week 4 the tumor burden for treated animals dropped to 0.4% (PET) and 3.6% (MRI) and in the case of control group the tumor burden increased to 34.2% (PET) and 31.3% (MRI).

Conclusions: We found that tumor burden as measured with FCH PET strongly correlates with MRI data. FCH PET provided better contrast in early stages of therapy since it reflects the metabolic changes of choline metabolism caused by the treatment.





This Article
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Right arrow Articles by Marik, J.
Right arrow Articles by Williams, S.
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Right arrow Articles by Marik, J.
Right arrow Articles by Williams, S.