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OtherClinical Investigations

Expression of Multidrug Resistance Protein and Messenger RNA Correlate with 99mTc-MIBI Imaging in Patients with Lung Cancer

Jinshan Zhou, Kotaro Higashi, Yoshimichi Ueda, Yuko Kodama, Dachuan Guo, Fumiko Jisaki, Aya Sakurai, Tsutomu Takegami, Shogo Katsuda and Itaru Yamamoto
Journal of Nuclear Medicine October 2001, 42 (10) 1476-1483;
Jinshan Zhou
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Kotaro Higashi
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Yoshimichi Ueda
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Yuko Kodama
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Dachuan Guo
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Fumiko Jisaki
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Aya Sakurai
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Tsutomu Takegami
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Shogo Katsuda
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Itaru Yamamoto
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  • FIGURE 1.
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    FIGURE 1.

    Patient 1, 73-y-old man with 2.8 × 2.8 cm lung adenocarcinoma. (A) CT scan shows nodule in right lung. (B) Early 99mTc-MIBI SPECT scan (left) shows intense uptake (arrow) of 99mTc-MIBI in tumor (L/Ne = 3.81). Delayed scan (right) shows faint 99mTc-MIBI uptake in tumor (L/Nd = 1.00), suggesting rapid washout of 99mTc-MIBI from tumor (L/Nwr = 73.8%). Immunohistochemistry (×200) reveals strong Pgp expression (C), strong MRP expression (D), and weak LRP expression (E) in corresponding tumor tissue.

  • FIGURE 2.
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    FIGURE 2.

    Patient 34, 68-y-old woman with 3.6 × 3.6 cm lung adenocarcinoma. (A) CT scan shows nodule in right lung. (B) Early 99mTc-MIBI SPECT scan (left) shows intense uptake of 99mTc-MIBI in tumor (L/Ne = 3.65). Delayed scan (right) also shows intense 99mTc-MIBI uptake in tumor (L/Nd = 5.17), suggesting slow washout of 99mTc-MIBI from tumor (L/Nwr = −41.6%). Immunohistochemistry (×200) reveals negative Pgp expression (C), negative MRP expression (D), and strong LRP expression (E) in corresponding tumor tissue.

  • FIGURE 3.
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    FIGURE 3.

    Relationship between expression of Pgp, MRP, or LRP and 99mTc-MIBI L/Nd in lung cancer. (A) L/Nd correlated inversely with density of Pgp expression. Statistically significant difference in L/Nd was found between Pgp (−) group and Pgp (++) group. (B) No significant difference (n.s.) in L/Nd was found among MRP (++), MRP (+), and MRP (−) groups. (C) No significant difference in L/Nd was found among LRP (++), LRP (+), and LRP (−) groups.

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    FIGURE 4.

    Relationship between expression of Pgp, MRP, or LRP and 99mTc-MIBI L/Nwr in lung cancer. (A) L/Nwr correlated with density of Pgp expression. Statistically significant difference in L/Nwr was found between Pgp (++) group and Pgp (−) group. (B) No significant difference (n.s.) in L/Nwr was found among MRP(++), MRP (+), and MRP (−) groups. (C) No significant difference in L/Nwr was found among LRP (++), LRP (+), and LRP (−) groups.

  • FIGURE 5.
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    FIGURE 5.

    Relationship between Pgp mRNA expression and 99mTc-MIBI L/Nd or 99mTc-MIBI L/Nwr in lung cancer. (A) L/Nd correlated inversely with Pgp mRNA level. Statistically significant difference in L/Nd was found between Pgp mRNA low-expression group and Pgp mRNA high-expression group. (B) Statistical support was found toward a significant difference in L/Nwr between Pgp mRNA high-expression group and Pgp mRNA low-expression group.

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    TABLE 1

    Oligonucleotides Used for PCR Amplifications

    GeneQuantification methodSequencecDNA
    MDR1Forward primer5′CCCAGGAGCCCATCCTGT3′3774-3791
    Reverse primer5′CCCGGCTGTTGTCTCCATA3′3838-3821
    Probe5′(FAM)TGACTGCAGCATTGCTGAGAACATTGC(TAMRA)3′3793-3819
    MRPForward primer5′AAGCGCCTCGAGTCGGT3′3617-3633
    Reverse primer5′TCGAATGACGCTGACCCC3′3694-3677
    Probe5′(FAM)AGCCGCTCCCCGGTCTATTCCC(TAMRA)3′3635-3656
    LRPForward primer5′TTTCGATGACTTCCATAAGAACTCA3′1881-1905
    Reverse primer5′TTCCGAGGTCTCAAAGCCAA3′1950-1931
    Probe5′(FAM)CCCGCATCATTCGCACTGCTGT(TAMRA)3′1907-1928
    GAPDHForward primer5′GAAGGTGAAGGTCGGAGTCA3′
    Reverse primer5′GAAGATGGTGATGGGA3′
    Probe5′(JOE)CAAGCTTCCCGTTCTCAGCC(TAMRA)3′
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    TABLE 2

    Patient Characteristics and Radionuclide Imaging Results

    Patient no.Age (y)SexHistologyTumor size (cm)99mTc-MIBI SPECTImmunohistochemistryRT PCR
    L/NeL/NdL/Nwr (%)PgpMRPLRPMDR1MRPLRP
    173MADE2.83.811.0073.8+++++0.54350.00280.0784
    259MMeta2.61.521.0034.2+++++———
    337MLarge7.02.181.3538.1++++———
    462FADE2.21.771.0043.5+++++———
    572FADE1.91.161.0013.8++−++———
    656MADE1.01.001.00NA++−++0.07070.00040.2489
    760MADE5.51.001.00NA++++0.09140.17500.1643
    870MSmall5.01.31.48−13.8++++———
    982MADE3.42.153.18−47.9+++++0.00350.04480.1035
    1074MADE3.21.932.58−33.7++++0.00190.00960.1386
    1174MADE2.71.881.709.6+++0.04270.16230.0976
    1278MADESQ1.82.781.0064.0++++0.04890.02770.0236
    1364FADE1.61.781.0043.8++++———
    1466MADE2.51.852.21−19.5++++0.10820.06861.2370
    1558MADE1.51.001.00NA++++———
    1672MADE2.31.001.00NA+++———
    1772MMeta1.51.001.00NA++−———
    1874FADE2.82.031.973.0++++———
    1972FADE1.21.001.00NA+−++———
    2058FADE2.81.001.00NA+−+———
    2166MADE2.83.992.3740.6−++++———
    2281MSCC3.02.294.10−79.0−++———
    2372MADE2.11.611.97−22.4−+++———
    2470MADESQ2.51.571.429.6−+++———
    2566FADE2.61.361.78−30.9−++———
    2678MADE4.01.331.54−15.8−+++0.00270.00450.0125
    2773MSCC2.72.091.4530.0−++———
    2876MADE4.03.372.9811.6−+−0.02780.02830.0409
    2976MADE1.81.921.749.4−++———
    3075MSCC3.22.801.8434.3−++———
    3166MSCC2.51.001.00NA−+−———
    3279MSmall2.22.501.9422.4−+−———
    3372MSCC2.81.631.2523.3−−−———
    3468FADE3.63.655.17−41.6−−++———
    • ADE = adenocarcinoma; Meta = metastatic lung tumor; Large = large cell carcinoma; NA = not applicable; small = small cell carcinoma; ADESQ = adenosquamous cell carcinoma; SCC = squamous cell carcinoma.

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Journal of Nuclear Medicine
Vol. 42, Issue 10
October 1, 2001
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Expression of Multidrug Resistance Protein and Messenger RNA Correlate with 99mTc-MIBI Imaging in Patients with Lung Cancer
Jinshan Zhou, Kotaro Higashi, Yoshimichi Ueda, Yuko Kodama, Dachuan Guo, Fumiko Jisaki, Aya Sakurai, Tsutomu Takegami, Shogo Katsuda, Itaru Yamamoto
Journal of Nuclear Medicine Oct 2001, 42 (10) 1476-1483;

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Expression of Multidrug Resistance Protein and Messenger RNA Correlate with 99mTc-MIBI Imaging in Patients with Lung Cancer
Jinshan Zhou, Kotaro Higashi, Yoshimichi Ueda, Yuko Kodama, Dachuan Guo, Fumiko Jisaki, Aya Sakurai, Tsutomu Takegami, Shogo Katsuda, Itaru Yamamoto
Journal of Nuclear Medicine Oct 2001, 42 (10) 1476-1483;
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