Sigma receptors are expressed in human non-small cell lung carcinoma
C S John1, W D Bowen, V M Varma
1Department of Radiology, George Washington University Medical Center, Washington, DC 20037, USA.
Abstract:
N-(2-piperidinoethyl)4-iodobenzamide), IPAB, was used to characterize sigma receptors in non-small cell lung cancer (NSCLC) cell lines. 125IPAB bound with high affinity to large cell carcinoma (NCI-H1299), adenocarcinoma (NCI-H838), and lung carcinoid (NCI-H727) cell lines. Specific IPAB binding was inhibited with high affinity by haloperidol (Ki = 0.6 nM), IPAB (Ki = 14 nM) and 1,3-ditolyl guanidine (DTG) (Ki = 40 nM). Relative to other receptor ligands, IPAB was not readily internalized at 37 degrees C. IPAB had little effect on the growth of NSCLC cells. Scintigraphic imaging studies using 131IPAB in nude mice bearing NCI-H838 xenografts visualized the tumor at 24 or 30 hours after injection. These results suggest that sigma receptors which are present on NSCLC cells may be used as external markers for imaging tumors in vivo.
Insights
N-(2-piperidinoethyl)4-iodobenzamide (IPAB) can identify sigma receptors on non-small cell lung cancer (NSCLC) cells. These receptors show potential as imaging markers for visualizing NSCLC tumors in vivo.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Sigma receptors are implicated in various cellular processes.
- Their role in non-small cell lung cancer (NSCLC) requires further elucidation.
- Targeted imaging agents are crucial for early cancer detection.
Purpose of the Study:
- To characterize sigma receptors in NSCLC cell lines using N-(2-piperidinoethyl)4-iodobenzamide (IPAB).
- To evaluate the potential of IPAB as an imaging biomarker for NSCLC.
Main Methods:
- Radioligand binding assays using 125IPAB on NSCLC cell lines (NCI-H1299, NCI-H838, NCI-H727).
- Inhibition studies with known sigma receptor ligands (haloperidol, DTG).
- In vivo scintigraphic imaging of NCI-H838 xenografts in nude mice using 131IPAB.
Main Results:
- 125IPAB demonstrated high-affinity binding to NSCLC cell lines.
- Specific binding was confirmed by inhibition studies.
- 131IPAB successfully visualized NSCLC tumors in vivo at 24-30 hours post-injection.
Conclusions:
- Sigma receptors are present on NSCLC cells.
- IPAB exhibits characteristics suitable for sigma receptor imaging.
- Sigma receptors may serve as valuable external markers for NSCLC tumor imaging.
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