Comparative antiproliferative effects of (111)In-DTPA-hEGF, chemotherapeutic agents and gamma-radiation on EGFR-positive breast cancer cells.
The antiproliferative effects of (111)In-DTPA-hEGF on breast cancer cells expressing high levels of EGFR were compared with those of chemotherapeutic agents or gamma-radiation. MDA-MB-468 cells were cultured with (111)In-DTPA-hEGF (30 MBq/microg, 1.8 x 10(5) MBq/micromol), DTPA-hEGF, methotrexate, doxorubicin, paclitaxel or 5-fluorouracil. Cell growth was measured colorimetrically. The IC(50) for 111In-DTPA-hEGF was < 70 pM (11 kBq/mL) versus 500 pM for DTPA-hEGF. The IC(50) for paclitaxel, methotrexate, doxorubicin and 5-fluorouracil was 6 nM, 15 nM, 20 nM and 4 microM respectively. (111)In-DTPA-hEGF (70 pM, 11 kBq/mL) delivered approx. 6 Gy to breast cancer cells producing growth inhibition equivalent to 4 Gy of gamma-radiation. We conclude that (111)In-DTPA-hEGF exhibited potent antiproliferative effects towards breast cancer cells at concentrations much lower than chemotherapeutic agents and equivalent to those produced by several Gy of high dose rate gamma-radiation.
Chen
Paul
P
Division of Nuclear Medicine, University Health Network, Toronto, ON, Canada M5G 2C4.
Mrkobrada
Marko
M
Vallis
Katherine A
KA
Cameron
Ross
R
Sandhu
Jasbir
J
Hendler
Aaron
A
Reilly
Raymond M
RM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D004317:Doxorubicin / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000627:therapeutic use; D066246:ErbB Receptors / Q000378:metabolism; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D004369:Pentetic Acid / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D004815:Epidermal Growth Factor; D004369:Pentetic Acid; D004317:Doxorubicin; D066246:ErbB Receptors; D008727:Methotrexate