 |
| Chemical name: | 89Zr-N-Succinyldesferrioxamine-DN30 | |
| Abbreviated name: | 89Zr-DN30 | |
| Synonym: | ||
| Agent category: | Antibody | |
| Target: | Mesenchymal-epithelial transition factor (MET), also known as the tyrosine kinase receptor for hepatocyte growth factor | |
| Target category: | Antigen | |
| Method of detection: | Positron emission tomography (PET) | |
| Source of signal: | 89Zr | |
| Activation: | No | |
| Studies: |
| No structure is available in PubChem. |
[PubMed]
MET (Mesenchymal-epithelial transition factor gene) is a proto-oncogene that encodes a protein MET, also known as c-Met or hepatocyte growth factor receptor (HGFR) (1). MET is a membrane receptor that is essential for embryonic development and wound healing. Hepatocyte growth factor (HGF) is the only known ligand of MET. MET is normally expressed by stem cells, progenitor cells, and cells of epithelial origin, whereas expression of HGF is restricted to cells of mesenchymal origin. Upon HGF stimulation, MET induces several biological responses that lead to invasive growth (2). Abnormal MET activation in cancer correlates with poor prognosis because deregulated MET triggers tumor growth, induces angiogenesis, and activates metastasis (3). MET is deregulated in many types of human malignancies, including kidney, liver, stomach, breast, and brain cancers (2, 4, 5). Monoclonal antibody DN30 is directed against the extracellular domain of MET with a dissociation constant (Kd) of 2.64 nM (6). Inhibition of HGFR function with DN30 has been shown to inhibit pathological angiogenesis as well as tumor growth and metastasis. Perk et al. (7) prepared 89Zr-N-succinyldesferrioxamine-DN30 (89Zr-DN30) for imaging MET expression in tumors.
[PubMed]
N-Succinyldesferrioxamine (N-sucDf) B-tetrafluorophenol-Fe and DN30 were incubated in sodium carbonate buffer (pH 9.5) for 30 min at room temperature (7). To the mixture, an ethylenediaminetetraacetic acid solution was added, and the mixture was incubated for 30 min at 35ºC. N-sucDf-DN30 was isolated from the incubation mixture with a PD-10 column, yielding approximately one chelate group per antibody. N-sucDf-DN30 was mixed with 89Zr-oxalate. The mixture was incubated at room temperature for 45 min. 89Zr-DN30 had a radiochemical purity of >95% and a specific activity of 8.2–10.6 MBq/nmol (0.22–0.29 mCi/nmol) with a labeling yield of >70%.
[PubMed]
Radioimmunoreactivity of 89Zr-DN30 for MET was determined by measuring 89Zr-DN30 binding to human gastric carcinoma cell line GTL-16 cells to be >95% at infinite antigen excess (7).
[PubMed]
Perk et al. (7) performed biodistribution studies of 0.28 MBq (0.008 mCi) 89Zr-DN30 (0.66 nmol) in nude mice bearing xenografts of GTL-16 (high MET expression) or the HNSCC cell line FaDu (low MET expression). GTL-16 tumor uptake values were 12.2% ID/g (percentage injected dose per gram) at 1 d, 17.3% ID/g at 2 d, 18.1% ID/g at 3 d, and 19.6% ID/g at 5 d. The radioactivity levels in the blood were 17.1, 13.3, 10.6, and 8.8% ID/g at 1, 2, 3, and 5 d, respectively. The organs with the highest uptake were the liver (8.4% ID/g), spleen (7.9% ID/g), lung (4.5% ID/g), and kidney (3.5% ID/g), with the lowest radioactivity in the muscle (1.2% ID/g) at 3 d after injection. The tumor/muscle ratio was 15. On the other hand, FaDu tumor uptake was lower than that of the GTL-16 tumor, with only 7.8% ID/g and a tumor/muscle ratio of 7 at 3 d. Positron emission tomography imaging revealed that GTL-16 tumors as small as 11 mg were readily visualized as early as 1 d and for up to 4 d after injection. The liver and spleen were also visualized. FaDu tumors were less pronounced than GTL-16 tumors. Immunohistochemistry with DN30 performed on GTL-16 and FaDu xenografts showed that the expression of MET was higher in the GTL-16 tumor sections than in the FaDu tumor sections. No blocking experiments were performed, but the use of a high expressing tumor and a low expression tumor supports the specificity of localization.
Download a summary of all MICAD entries as a comma-separated-values file containing the fields:
Chemical name
Abbreviated name
Synonym
Agent category
Target
Target category
Method of detection
Source of signal / contrast
Activation
Studies
PubChem links
Nucleotide links
Protein links
Gene links
MICAD URL
