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OtherBASIC SCIENCE INVESTIGATIONS

Methotrexate, Paclitaxel, and Doxorubicin Radiosensitize HER2-Amplified Human Breast Cancer Cells to the Auger Electron–Emitting Radiotherapeutic Agent 111In-NLS-Trastuzumab

Danny L. Costantini, Daniela F. Villani, Katherine A. Vallis and Raymond M. Reilly
Journal of Nuclear Medicine March 2010, 51 (3) 477-483; DOI: https://doi.org/10.2967/jnumed.109.069716
Danny L. Costantini
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Daniela F. Villani
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Katherine A. Vallis
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Raymond M. Reilly
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  • FIGURE 1. 
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    FIGURE 1. 

    SFs of MDA-MB-231, 231-H2N, TrR1, and TrR2 human breast cancer cells after treatment with 111In-NLS-trastuzumab alone (radioimmunotherapy [RIT]) (∼0.2 MBq/μg, 100 nmol/L) or 111In-NLS-trastuzumab combined with IC10 concentrations of methotrexate (MTX) (RIT + MTX ), paclitaxel (PAC) (RIT + PAC), or doxorubicin (DOX) (RIT + DOX). IC10 values of each drug for each cell line are shown in Table 1. *P < 0.05, compared with RIT.

  • FIGURE 2. 
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    FIGURE 2. 

    (A) Residual γH2AX-foci in MDA-MB-231, 231-H2N, TrR1, and TrR2 human breast cancer cells 24 h after exposure to 111In-NLS-trastuzumab alone (radioimmunotherapy [RIT]) (100 nmol/L) or 111In-NLS-trastuzumab combined with IC10 concentrations of methotrexate (MTX) (RIT + MTX), paclitaxel (PAC) (RIT + PAC), or doxorubicin (DOX) (RIT + DOX). Number of γH2AX-foci per nucleus is shown as mean ± SEM, and at least 30 nuclei were assessed for γH2AX-foci for each treatment. (B) Induction of γH2AX-foci (green) 24 h after exposure to 111In-NLS-trastuzumab alone or concurrently with MTX, PAC, or DOX. Nuclear DNA was stained with DAPI (blue). *P < 0.05, compared with control, or **P < 0.05, compared with 111In-NLS-trastuzumab.

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    TABLE 1

    IC10 and IC50 Values for Methotrexate, Paclitaxel, and Doxorubicin on MDA-MB-231, 231-H2N, TrR1, and TrR2 Human Breast Cancer Cells

    Cell lineMethotrexate*PaclitaxelDoxorubicin
    MDA-MB-231
     IC10 (μmol/L)1.01 ± 0.010.07 ± 0.030.19 ± 0.08
     IC50 (μmol/L)103.3 ± 13.40.32 ± 0.131.26 ± 0.39
    231-H2N
     IC10 (μmol/L)12.0 ± 0.230.14 ± 0.100.02 ± 0.004
     IC50 (μmol/L)120.8 ± 23.31.36 ± 0.240.16 ± 0.04
    TrR1
     IC10 (μmol/L)0.01 ± 0.0010.12 ± 0.030.03 ± 0.01
     IC50 (μmol/L)0.13 ± 0.012.01 ± 0.470.55 ± 0.25
    TrR2
     IC10 (μmol/L)1.13 ± 0.160.02 ± 0.010.02 ± 0.003
     IC50 (μmol/L)102.4 ± 10.70.27 ± 0.060.21 ± 0.08
    • ↵* Values were reported previously in Costantini et al. (16).

    • Results are expressed as mean ± SEM of 3 measurements performed in duplicate.

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    TABLE 2

    Radiation Enhancement Ratio (RER) for Methotrexate, Paclitaxel, and Doxorubicin on Human Breast Cancer Cells When Combined with 111In-NLS-Trastuzumab

    Cell lineMethotrexatePaclitaxelDoxorubicin
    MDA-MB-2311.01.01.1
    231-H2N2.21.62.7
    TrR12.01.82.8
    TrR21.01.01.0
    • RERs were determined by dividing SF of cells treated with 111In-NLS-trastuzumab alone (∼0.2 MBq/μg, 100 nmol/L) by that of cells treated concurrently with 111In-NLS-trastuzumab and IC10 dose for methotrexate, paclitaxel, or doxorubicin. IC10 values for each drug on each cell line are shown in Table 1.

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Journal of Nuclear Medicine: 51 (3)
Journal of Nuclear Medicine
Vol. 51, Issue 3
March 2010
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Methotrexate, Paclitaxel, and Doxorubicin Radiosensitize HER2-Amplified Human Breast Cancer Cells to the Auger Electron–Emitting Radiotherapeutic Agent 111In-NLS-Trastuzumab
Danny L. Costantini, Daniela F. Villani, Katherine A. Vallis, Raymond M. Reilly
Journal of Nuclear Medicine Mar 2010, 51 (3) 477-483; DOI: 10.2967/jnumed.109.069716

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Methotrexate, Paclitaxel, and Doxorubicin Radiosensitize HER2-Amplified Human Breast Cancer Cells to the Auger Electron–Emitting Radiotherapeutic Agent 111In-NLS-Trastuzumab
Danny L. Costantini, Daniela F. Villani, Katherine A. Vallis, Raymond M. Reilly
Journal of Nuclear Medicine Mar 2010, 51 (3) 477-483; DOI: 10.2967/jnumed.109.069716
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