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Issue 9, 2014
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Synthesis and biological evaluation of panitumumab–IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers

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Abstract

To investigate panitumumab–IRDye800 as an intraoperative optical imaging agent for epidermal growth factor receptor (EGFR)-expressing cancers, we developed clinical-quality panitumumab–IRDye800 and evaluated its specificity and sensitivity to visualize tumors by fluorescence imaging in a variety of mouse xenograft models with different levels of EGFR-expression. Panitumumab was chemically conjugated to NIR-dye (Li-COR 800CW) at well-defined and limited substitution ratio (1 : 1–2) for the characterization of fluorescence signals. The yield and purity of the conjugate was 80 ± 5% and 95 ± 2%, respectively (n = 6). Quality control (QC) tests showed that the product was suitable for clinical development. Female athymic nude xenograft tumor bearing mice (n = 5 per tumor model) with very low (BT-474), moderate (MDA-MB-231), and high (MDA-MB-468) EGFR-expression levels were administered panitumumab–IRDye800 formulations (100 μg of mAb in 100 μL of 0.9% saline) via tail-vein injection. Animal imaging and biodistribution experiments were conducted on an FMT 2500 (Perkin Elmer) fluorescence scanner at 24, 48, 72, 96, and 144 hours post-injection. Immuno-fluorescence images of a panitumumab–IRDye conjugate recorded in mouse xenograft models showed a good correlation (R2 = 0.91) between EGFR-expression level and tumor uptake. Uptake of panitumumab labeled with IR-Dye or [89Zr] in different tumor xenografts with high, medium, and low EGFR expression, as measured by fluorescence or radioactive counts, is highly correlated (r2 = 0.99). This preclinical in vivo study proved that panitumumab–IRDye800 is specific and optical imaging in conjunction with this probe is sensitive enough to detect EGFR-expressing tumors.

Graphical abstract: Synthesis and biological evaluation of panitumumab–IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers

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Publication details

The article was received on 13 Mar 2014, accepted on 28 May 2014 and first published on 30 May 2014


Article type: Concise Article
DOI: 10.1039/C4MD00116H
Citation: Med. Chem. Commun., 2014,5, 1337-1346
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    Synthesis and biological evaluation of panitumumab–IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancers

    S. Bhattacharyya, N. L. Patel, L. Wei, L. A. Riffle, J. D. Kalen, G. C. Hill, P. M. Jacobs, K. R. Zinn and E. Rosenthal, Med. Chem. Commun., 2014, 5, 1337
    DOI: 10.1039/C4MD00116H

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