Abstract
Cyclooxygenase-2 (COX-2) plays an important role in angiogenesis and cancer progression. Since many tumor cells exhibit COX-2 expression, functional imaging of COX-2 expression using celebrex (CBX, a COX-2 inhibitor) may provide not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-COX-2 therapy could also be assessed effectively. This study aimed at measuring uptake of 99mTc-EC-CBX in COX-2 expression in tumor-bearing animal models. In vitro Western blot analysis and cellular uptake assays were used to examine the feasibility of using 99mTc-EC-CBX to measure COX-2 activity. Tissue distribution studies of 99mTc-EC-CBX were evaluated in tumor-bearing rodents at 0.5-4 h. Dosimetric absorption was then estimated. Planar scintigraphy was performed in mice, rats and rabbits bearing tumors. In vitro cellular uptake indicated that cells with higher COX-2 expression (A549 and 13762) had higher uptake of 99mTc-EC-CBX than lower COX-2 expression (H226). In vivo biodistribution of 99mTc-EC-CBX in tumor-bearing rodents showed increased tumor:tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-CBX to assess COX-2 expression. Planar images confirmed that the tumors could be visualized with 99mTc-EC-CBX from 0.5 to 4 h in tumor-bearing animal models. We conclude that 99mTc-EC- CBX may be useful to assess tumor COX-2 expression. This may be useful in the future for selecting patients for treatment with anti-COX-2 agents. copy; 2004 Lippincott Williams & Wilkins.
Original language | English (US) |
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Pages (from-to) | 255-263 |
Number of pages | 9 |
Journal | Anti-cancer drugs |
Volume | 15 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2004 |
Keywords
- COX-2 imaging
- Tc-EC-celebrex
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)
- Cancer Research