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Technetium-99m-hexakis-2-methoxyisobutylisonitrile scintigraphy and multidrug resistance-related protein expression
Xiao-Yi Duan1, Jian-Sheng Wang, Min Liu
1Department of Nuclear Medicine, The First Affiliated Hospital, Medical College, Xi'an Jiaotong University, No. 1 Jiankang Road, Xi'an, Shaanxi, 710061, China. duanxy@mail.xjtu.edu.cn
Objective:
The occurrence of multidrug resistance (MDR) is a major cause of resistance to chemotherapeutic agents in patients with lung cancer, in part owing to the overexpression of MDR-related proteins. Technetium-99m-hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been shown to be a substrate for some MDR-related proteins. The aim of this study is to evaluate the role of (99m)Tc-MIBI scintigraphy for functional imaging of MDR-related protein phenotypes.
Methods:
To determine the correlation between (99m)Tc-MIBI scintigraphy and the expression level of P-glycoprotein (Pgp), multidrug-resistance protein (MRP), and glutathione-S-transferase Pi (GSTpi), 26 patients (17 men and 9 women, median age 57.5 years) with primary lung cancer were investigated. Following intravenous administration of 925 MBq (99m)Tc-MIBI, single-photon emission computed tomography (SPECT) and computed tomography (CT) were performed at 15 min and 2 h. On the basis of the fused images, tumor to background (T/B) ratio of both early and delayed images, and washout rate (WR%) of (99m)Tc-MIBI were calculated. The immunohistochemical staining of Pgp, MRP, and GSTpi was performed, and the expression level was semiquantitated using a pathoimage analysis system. The imaging results were compared with the status of Pgp, MRP, and GSTpi expression.
Results:
The WR% of (99m)Tc-MIBI showed a significant positive correlation with Pgp expression (r = 0.560, P = 0.003), as no correlation was observed between WR% and MRP or GSTpi (r = 0.354, P = 0.076; r = 0.324, P = 0.106). Neither early T/B nor delayed T/B correlated with the expression level of Pgp, MRP, and GSTpi. WR%, Pgp, and GSTpi expression showed significant differences between squamous cell carcinoma (group A) and adenocarcinoma (group B). There was no significant difference among Pgp, MRP, and GSTpi expression levels in any cases (P > 0.05).
Conclusions:
Our data confirmed that (99m)Tc-MIBI scintigraphy is useful for determining the MDR caused by Pgp in patients with primary lung cancer.
Insights
Technetium-99m-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy effectively identifies P-glycoprotein-mediated multidrug resistance (MDR) in lung cancer. This functional imaging tool aids in assessing MDR phenotypes, crucial for treatment resistance.
Area of Science:
- Nuclear Medicine
- Oncology
- Molecular Imaging
Background:
- Multidrug resistance (MDR) significantly impacts lung cancer treatment outcomes.
- Overexpression of MDR-related proteins contributes to chemotherapy resistance.
- Technetium-99m-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for several MDR proteins.
Purpose of the Study:
- To evaluate the utility of 99mTc-MIBI scintigraphy for functional imaging of MDR-related protein phenotypes in lung cancer.
- To correlate 99mTc-MIBI uptake and washout patterns with the expression of key MDR proteins.
Main Methods:
- 26 primary lung cancer patients underwent 99mTc-MIBI SPECT/CT imaging.
- Tumor-to-background ratios and washout rates (WR%) were calculated.
- Immunohistochemical staining assessed P-glycoprotein (Pgp), MRP, and GSTpi expression.
Main Results:
- A significant positive correlation was found between 99mTc-MIBI WR% and Pgp expression (r=0.560, P=0.003).
- No significant correlation was observed between WR% and MRP or GSTpi expression.
- Significant differences in WR%, Pgp, and GSTpi expression were noted between squamous cell carcinoma and adenocarcinoma subtypes.
Conclusions:
- 99mTc-MIBI scintigraphy is a valuable tool for assessing Pgp-mediated MDR in primary lung cancer.
- This functional imaging approach can help characterize MDR phenotypes and inform treatment strategies.
