Expression of multidrug resistance protein and messenger RNA correlate with (99m)Tc-MIBI imaging in patients with lung cancer.

Abstract

UNLABELLED:

In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance-associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer.

METHODS:

Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression.

RESULTS:

The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA.

CONCLUSION:

These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of (99m)Tc-MIBI in lung cancer.

• Authors: J Zhou, K Higashi, Y Ueda, Y Kodama, D Guo, F Jisaki, A Sakurai, T Takegami, S Katsuda, I Yamamoto
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 42 Issue 10 Pg. 1476-83 (Oct 2001) ISSN: 0161-5505 [Print] United States
• PMID: 11585860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP-Binding Cassette Transporters
• Multidrug Resistance-Associated Proteins
• Neoplasm Proteins
• RNA, Messenger
• Radiopharmaceuticals
• Vault Ribonucleoprotein Particles
• major vault protein
• Technetium Tc 99m Sestamibi

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• ATP-Binding Cassette Transporters (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Drug Resistance, Multiple
• Female
• Humans
• Immunohistochemistry
• Lung Neoplasms (diagnostic imaging, metabolism)
• Male
• Middle Aged
• Multidrug Resistance-Associated Proteins
• Neoplasm Proteins (metabolism)
• RNA, Messenger (metabolism)
• Radiopharmaceuticals
• Reverse Transcriptase Polymerase Chain Reaction
• Technetium Tc 99m Sestamibi
• Tomography, Emission-Computed, Single-Photon
• Vault Ribonucleoprotein Particles (metabolism)