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


CONCLUSIONS
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.
Zhou
J
J
Department of Radiology, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan.
Higashi
K
K
Ueda
Y
Y
Kodama
Y
Y
Guo
D
D
Jisaki
F
F
Sakurai
A
A
Takegami
T
T
Katsuda
S
S
Yamamoto
I
I
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D019275:Radiopharmaceuticals; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein