Abstract | UNLABELLED: METHODS:
Breast cancer cell lines with a range of EGFR expression levels were exposed to 111In-DTPA-hEGF or gamma-radiation. The cell lines (followed by number of EGFR per cell in parentheses) were MDA-MB-468 (1.3 x 10(6)), MDA-MB-231 (1.3 x 10(5)), and MCF-7 (1.5 x 10(4)). The proportion of radioactivity partitioning into the nucleus was measured by cell fractionation. DNA double-strand breaks were evaluated using the gamma-H2AX assay. Clonogenic survival assays were used to measure cytotoxicity. RESULTS: All data are presented as mean +/- SD. The amount of 111In-DTPA-hEGF that translocated to the nucleus (in mBq/nucleus) in MDA-MB-468, MDA-MB-231, and MCF-7 cells incubated with 111In-DTPA-hEGF (5.2 MBq/mL, 43 nM) for 20 h was 131 +/- 6, 8.1 +/- 0.1, and 1.1 +/- 0.9, respectively. The number of gamma-H2AX foci per nucleus was 35 +/- 15, 19 +/- 10, and 1.7 +/- 0.3, respectively. A reduction in the surviving fraction (SF) in MDA-MB-468 (0.013 +/- 0.001) and MDA-MB-231 (0.5 +/- 0.1) but not in MCF-7 cells after exposure to 111In-DTPA-hEGF (5.2 MBq/mL, 43 nM) for 20 h has been demonstrated. The SF of MDA-MB-468 cells after exposure to DTPA- EGF (43 nM) and 111In-acetate (5.2 MBq/mL) for 20 h was 0.5 +/- 0.1 and 0.53 +/- 0.05, respectively. MDA-MB-468 was the most sensitive of the cell lines to gamma-irradiation, with an SF after 2 Gy of 0.45 +/- 0.04, compared with 0.7 +/- 0.1 and 0.8 +/- 0.1 for MCF-7 and MDA-MB-231, respectively. The number of gamma-H2AX foci per nucleus in MDA-MB-468 cells correlated with the concentration, specific activity, and incubation time of 111In-DTPA-hEGF. CONCLUSION: DNA damage caused by 111In-DTPA-hEGF correlates with the EGFR expression level of the exposed cells and with concentration, specific activity, and incubation time of 111In-DTPA-hEGF. The gamma-H2AX assay may be a useful biomarker to predict and monitor the outcome of treatment with 111In-DTPA-hEGF.
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Authors | Zhongli Cai, Zhuo Chen, Kristy E Bailey, Deborah A Scollard, Raymond M Reilly, Katherine A Vallis |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 49
Issue 8
Pg. 1353-61
(Aug 2008)
ISSN: 0161-5505 [Print] United States |
PMID | 18632822
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 111In-DTPA-human epidermal growth factor
- H2AX protein, human
- Histones
- Indium Radioisotopes
- Radiopharmaceuticals
- Epidermal Growth Factor
- Pentetic Acid
- ErbB Receptors
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Topics |
- Active Transport, Cell Nucleus
- Breast Neoplasms
- Cell Line, Tumor
- Cell Nucleus
(metabolism)
- Cell Survival
(drug effects, radiation effects)
- DNA Damage
- Epidermal Growth Factor
(metabolism, pharmacology)
- ErbB Receptors
(biosynthesis)
- Female
- Gamma Rays
- Histones
(biosynthesis)
- Humans
- Indium Radioisotopes
- Pentetic Acid
(analogs & derivatives, metabolism, pharmacology)
- Phosphorylation
- Radiopharmaceuticals
(metabolism, pharmacology)
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