Universität zu Köln

Kanefendt, Friederike, Lindauer, Andreas, Mross, Klaus, Fuhr, Uwe and Jaehde, Ulrich (2012). Determination of soluble vascular endothelial growth factor receptor 3 (sVEGFR-3) in plasma as pharmacodynamic biomarker. J. Pharm. Biomed. Anal., 70. S. 485 - 492. AMSTERDAM: ELSEVIER. ISSN 1873-264X

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Abstract

Soluble VEGFR-3 (sVEGFR-3) is a potential biomarker for the anti-angiogenic activity of tyrosine kinase inhibitors. The aim of this investigation was the validation of an enzyme-linked immunosorbent assay (ELISA) to measure sVEGFR-3 in human plasma and the investigation of its applicability in clinical trials as first step of the biomarker validation process. General validation criteria were assessed based on current guidelines and recommendations for immunoassays. The ELISA was applied in two clinical trials including healthy volunteers and metastatic colorectal cancer (mCRC) patients receiving 50 or 37.5 mg sunitinib per day, respectively. SVEGFR-3 was measured at predefined time points. Undiluted, inactivated fetal calf serum was identified as surrogate matrix to substitute for human plasma. Dilutional linearity and parallelism could be successfully confirmed. The analyte was measured in the study matrix with intra- and inter-run precision and accuracy <= 20%. Stability was proven over a period of at least 15 months as well as upon three freeze-thaw cycles. SVEGFR-3 concentrations decreased in response to sunitinib to 57% (IQR 50-88%) and 58% (IQR 47-80%) of the respective baseline concentrations in healthy volunteers and mCRC patients, respectively, with subsequent increase after stop of treatment. The ELISA for the quantification of sVEGFR-3 in human plasma was successfully validated. The applicability of the assay was demonstrated in two clinical trials. (C) 2012 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kanefendt, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Lindauer, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mross, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaehde, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480071
DOI:	10.1016/j.jpba.2012.06.039
Journal or Publication Title:	J. Pharm. Biomed. Anal.
Volume:	70
Page Range:	S. 485 - 492
Date:	2012
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1873-264X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language METASTATIC COLORECTAL-CANCER; ANTI-ANGIOGENIC AGENTS; RENAL-CELL CARCINOMA; PHASE-II; PROTEIN BIOMARKERS; METHOD VALIDATION; SUNITINIB; INHIBITOR; EFFICACY; SU11248 Multiple languages Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48007