Abstract
The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [ 11C]4a-c and [ 11C]8a-d, were prepared by O-[ 11C] methylation of their corresponding precursors using [ 11C]CH 3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC 50 values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 4760-4767 |
| Number of pages | 8 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 46 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2011 |
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Keywords
- Cancer imaging
- Carbon-11-labeled celecoxib derivatives
- Cyclooxygenase-2 (COX-2)
- Positron emission tomography (PET)
- Radiotracers
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Pharmacology
Cite this
Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer. / Gao, Mingzhang; Wang, Min; Miller, Kathy; Zheng, Qi-Huang.
In: European Journal of Medicinal Chemistry, Vol. 46, No. 9, 09.2011, p. 4760-4767.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer
AU - Gao, Mingzhang
AU - Wang, Min
AU - Miller, Kathy
AU - Zheng, Qi-Huang
PY - 2011/9
Y1 - 2011/9
N2 - The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [ 11C]4a-c and [ 11C]8a-d, were prepared by O-[ 11C] methylation of their corresponding precursors using [ 11C]CH 3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC 50 values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.
AB - The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [ 11C]4a-c and [ 11C]8a-d, were prepared by O-[ 11C] methylation of their corresponding precursors using [ 11C]CH 3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% (n = 5) and 57 ± 3% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5). The IC 50 values to block COX-2 for known compounds celecoxib (4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a-d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer.
KW - Cancer imaging
KW - Carbon-11-labeled celecoxib derivatives
KW - Cyclooxygenase-2 (COX-2)
KW - Positron emission tomography (PET)
KW - Radiotracers
UR - http://www.scopus.com/inward/record.url?scp=80052920865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052920865&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2011.05.024
DO - 10.1016/j.ejmech.2011.05.024
M3 - Article
VL - 46
SP - 4760
EP - 4767
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 9
ER -