Use of a Single Hybrid Imaging Agent for Integration of Target Validation with In Vivo and Ex Vivo Imaging of Mouse Tumor Lesions Resembling Human DCIS

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Use of a Single Hybrid Imaging Agent for Integration of Target Validation with In Vivo and Ex Vivo Imaging of Mouse Tumor Lesions Resembling Human DCIS

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Title: Use of a Single Hybrid Imaging Agent for Integration of Target Validation with In Vivo and Ex Vivo Imaging of Mouse Tumor Lesions Resembling Human DCIS
Author: Buckle, Tessa; Kuil, Joeri; van den Berg, Nynke S.; Bunschoten, Anton; Lamb, Hildo J.; Yuan, Hushan; Josephson, Lee; Jonkers, Jos; Borowsky, Alexander D.; van Leeuwen, Fijs W. B.

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Citation: Buckle, Tessa, Joeri Kuil, Nynke S. van den Berg, Anton Bunschoten, Hildo J. Lamb, Hushan Yuan, Lee Josephson, Jos Jonkers, Alexander D. Borowsky, and Fijs W. B. van Leeuwen. 2013. Use of a single hybrid imaging agent for integration of target validation with in vivo and ex vivo imaging of mouse tumor lesions resembling human DCIS. PLoS ONE 8(1): e48324.
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Abstract: Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker. Methods: A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry–based target validation in fresh tumor tissue to \(in\) \(vivo\) single photon emission computed tomography (SPECT) imaging and \(in\) \(vivo\) and \(ex\) \(vivo\) fluorescence imaging. Results: Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4\(^{basal}\), CXCR4\(^+\) and CXCR4\(^{++}\) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry. Conclusion: The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches.
Published Version: doi:10.1371/journal.pone.0048324
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543428/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10859968
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