Loading...
Please wait, while we are loading the content...
Similar Documents
Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Oltenfreiter, Ruth Staelens, Ludovicus Kersemans, Veerle Cornelissen, B. M. Frankenne, Françis Foidart, J. -M. Wiele, Christophe Van De Slegers, Guido |
| Copyright Year | 2006 |
| Abstract | Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70 +/- 5% (n = 6) and 60 +/- 5% (n = 4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2. 0+/- 0.7%ID/g (3 h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48 h p.i. for 1'. For compound 2' a tumor uptake of 0.7 +/- 0.2%ID/g (3 h p.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24 h p.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2 h p.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary. |
| Starting Page | 27 |
| Ending Page | 30 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://orbi.ulg.ac.be/bitstream/2268/9933/1/Oltenfreiter%20ARI%202006.pdf |
| PubMed reference number | 16546398v1 |
| Volume Number | 64 |
| Issue Number | 6 |
| Journal | Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Body tissue Collagen Type IV Fibrillar Collagen Gelatinases Laminin Matrix Metalloproteinase Inhibitors Matrix Metalloproteinases Mercury Metalloproteases Muscle Neoplasms Non-Fibrillar Collagens Radiopharmaceuticals Serotonin Uptake Inhibitors Tracer Tritium Valine cancer cell carboxylesterase tumor tissue |
| Content Type | Text |
| Resource Type | Article |
