Abstract | UNLABELLED: METHODS: Peritoneal or omental biopsies obtained from women diagnosed with stage I, stage II, or stage III/IV ovarian cancer were evaluated by immunohistochemistry. The effects of carboplatin on mesothelial VCAM-1 expression were determined in cultured cells by Western blot. Radiolabeled VCAM-1-specific peptide imaging probes and SPECT were used in a mouse model of ovarian cancer peritoneal metastasis to identify VCAM-1 as a viable imaging target. RESULTS:
VCAM-1 expression correlated with tumor stage. All specimens from stage I patients were negative, whereas 29% of stage II patients and 73% of stage III/IV patients were positive. Although most women with advanced stage disease expressed VCAM-1, the incidence of expression was reduced among women who received neoadjuvant chemotherapy, suggesting a role for chemotherapy in regulating VCAM-1 expression. Treatment of mesothelial cells in culture with carboplatin resulted in a transient decrease in VCAM-1 expression 4 h after treatment that returned to baseline within 16-24 h. In vivo imaging of VCAM-1 also demonstrated an acute decrease in expression 4 h after carboplatin administration that recovered within 48 h in mice harboring platinum-resistant tumors. Chronic VCAM-1 expression reflected the effect of platinum-based treatment on tumor burden. Specifically, carboplatin treatment of mice with platinum-sensitive tumors showed reduced VCAM-1 expression, which correlated with reduced tumor burden; mice with platinum-resistant tumors retained elevated VCAM-1 expression and tumor burden after treatment. CONCLUSION: Clinically relevant VCAM-1-specific imaging probes identify VCAM-1 expression as an indicator of ovarian cancer peritoneal metastasis and therapeutic response to platinum-based agents. These observations support testing the utility of VCAM-1 imaging probes to monitor treatment response in ovarian cancer patients, thus providing the potential to improve management of women with this disease.
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Authors | Jennifer M Scalici, Stephanie Thomas, Christine Harrer, Timothy A Raines, Joanna Curran, Kristen A Atkins, Mark R Conaway, Linda Duska, Kimberly A Kelly, Jill K Slack-Davis |
Journal | Journal of nuclear medicine : official publication, Society of Nuclear Medicine
(J Nucl Med)
Vol. 54
Issue 11
Pg. 1883-9
(Nov 2013)
ISSN: 1535-5667 [Electronic] United States |
PMID | 24029657
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- Vascular Cell Adhesion Molecule-1
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Topics |
- Animals
- Biomarkers, Tumor
(genetics, metabolism)
- Cell Line, Tumor
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Mice
- Middle Aged
- Neoplasm Metastasis
- Ovarian Neoplasms
(diagnostic imaging, metabolism, pathology, therapy)
- Retrospective Studies
- Tomography, Emission-Computed, Single-Photon
- Treatment Outcome
- Vascular Cell Adhesion Molecule-1
(genetics, metabolism)
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