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Mol Imaging Biol. 2013 Apr;15(2):203-11. doi: 10.1007/s11307-012-0580-0.

Preclinical evaluation of a novel c-Met inhibitor in a gastric cancer xenograft model using small animal PET.

Author information

1
Department of Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner Siemens-Foundation, Eberhard Karls University Tübingen, Tübingen, Germany. stefan.wiehr@med.uni-tuebingen.de

Abstract

PURPOSE:

Here, we describe the efficacy of the novel small molecule c-Met inhibitor BAY 853474 in reducing tumor growth in the Hs746T gastric cancer xenograft model and tested the suitability of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) versus 3'-deoxy-3'-18F-fluorothymidine ([(18)F]FLT) for response monitoring in a gastric cancer xenograft mouse model using small animal PET.

PROCEDURES:

The c-Met inhibitor or vehicle control was administered orally at various doses in tumor-bearing mice. Glucose uptake and proliferation was measured using PET before, 48 and 96 h after the first treatment. The PET data were compared to data from tumor growth curves, autoradiography, Glut-1 and Ki-67 staining of tumor sections, and biochemical analysis of tissue probes, i.e., c-Met and ERK phosphorylation and cyclin D1 levels.

RESULTS:

BAY 853474 significantly reduces tumor growth. [(18)F]FDG uptake in Hs746T tumors was significantly reduced in the groups receiving the drug, compared with the control group. The [(18)F]FLT uptake in the tumor tissue was completely absent 96 h after treatment. Autoradiographic, immunohistochemical, and biochemical analyses confirmed the PET findings. Treatment with the c-Met inhibitor did not affect body weight or glucose levels, and no adverse effects were observed in the animals.

CONCLUSION:

These preclinical findings suggest that clinical PET imaging is a useful tool for early response monitoring in clinical studies.

PMID:
22864665
DOI:
10.1007/s11307-012-0580-0
[Indexed for MEDLINE]

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