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Imaging agents for in vivo molecular profiling of disseminated prostate cancer - targeting EGFR receptors in prostate cancer: Comparison of cellular processing of [In-111]-labeled affibody molecule Z(EGFR:2377) and cetuximab
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Orlova)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Tolmachev)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (Orlova)ORCID iD: 0000-0001-6120-2683
2011 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 4, p. 1137-1143Article in journal (Refereed) Published
Abstract [en]

Expression of receptor tyrosine-kinase (RTK) EGFR is low in normal prostate, but increases in prostate cancer. This receptor is significantly up-regulated as tumors progress into higher grade, androgen-insensitive and metastatic lesions. The up-regulated receptors could serve as targets for novel selective anti-cancer drugs, e.g. antibodies and tyrosine kinase inhibitors. Radionuclide imaging of RTK can facilitate patient stratification and monitoring of anti-RTK therapy of prostate cancer. The goal of the study was to evaluate binding and cellar processing of radiolabeled EGFR-targeting conjugates by prostate cancer cell lines. Receptor expression of EGFR was studied in three prostate cancer cell lines: DU145 (brain metastasis of PC, hormone insensitive), PC3 (bone metastasis of PC) and LNCaP (lymph node metastasis of PC, androgen and estrogen receptor positive). Uptake and internalization of anti-EGFR mAbs (cetuximab) and affibody molecule (Z2377) labeled with indium-111 was investigated. EGFR expression on prostate cancer cell lines was clearly demonstrated. Both labelled conjugates 111In-Z2377 and 111In-cetuximab bound to prostate cancer cells in the receptor mediated model. Expression levels were modest but correlate with degree of hormone independence. Internalization of Affibody molecules was relatively slow in all cell lines. Internalization of mAbs was more rapid. The level of EGFR expression in these cell lines is sufficient for in vivo molecular imaging. Slow internalization indicates possibility of the use of non-residualizing labels for affibody molecules.

Place, publisher, year, edition, pages
2011. Vol. 38, no 4, p. 1137-1143
Keywords [en]
prostate cancer, EGFR, HERI, imaging, affibody, cetuximab, DU-145, PC3, LNCaP
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-147607DOI: 10.3892/ijo.2011.915ISI: 000288581100026PubMedID: 21253675OAI: oai:DiVA.org:uu-147607DiVA, id: diva2:400559
Available from: 2011-02-26 Created: 2011-02-26 Last updated: 2017-12-11Bibliographically approved

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