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

被引:24
作者
Bhattacharyya, Sibaprasad [1 ]
Patel, Nimit L. [2 ]
Wei, Ling [1 ]
Riffle, Lisa A. [2 ]
Kalen, Joseph D. [2 ]
Hill, G. Craig [3 ]
Jacobs, Paula M. [4 ]
Zinn, Kurt R. [5 ]
Rosenthal, Eben [5 ]
机构
[1] Leidos Biomed Res, FNLCR, ADRD, Frederick, MD 21702 USA
[2] Leidos Biomed Res, FNLCR, SAIP, Frederick, MD 21702 USA
[3] Leidos Biomed Res, FNLCR, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD 21702 USA
[4] NCI, CIP, DCTD, Bethesda, MD 20892 USA
[5] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA
基金
美国国家卫生研究院;
关键词
MONOCLONAL-ANTIBODY; GUIDED SURGERY; BREAST-CANCER; TOMOGRAPHY; CARCINOMA; HEAD; PET;
D O I
10.1039/c4md00116h
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 mu g of mAb in 100 mu L 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 (R-2 = 0.91) between EGFR-expression level and tumor uptake. Uptake of panitumumab labeled with IR-Dye or [Zr-89] in different tumor xenografts with high, medium, and low EGFR expression, as measured by fluorescence or radioactive counts, is highly correlated (r(2) = 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.
引用
收藏
页码:1337 / 1346
页数:10
相关论文
共 15 条
[1]   Synthesis and evaluation of near-infrared (NIR) dye-herceptin conjugates as photoacoustic computed tomography (PCT) probes for HER2 expression in breast cancer [J].
Bhattacharyya, Sibaprasad ;
Wang, Shuyan ;
Reinecke, Daniel ;
Kiser, William, Jr. ;
Kruger, Robert A. ;
DeGrado, Timothy R. .
BIOCONJUGATE CHEMISTRY, 2008, 19 (06) :1186-1193
[2]   Zirconium-89 labeled panitumumab: a potential immuno-PET probe for HER1-expressing carcinomas [J].
Bhattacharyya, Sibaprasad ;
Kurdziel, Karen ;
Wei, Ling ;
Riffle, Lisa ;
Kaur, Gurmeet ;
Hill, G. Craig ;
Jacobs, Paula M. ;
Tatum, James L. ;
Doroshow, James H. ;
Kalen, Joseph D. .
NUCLEAR MEDICINE AND BIOLOGY, 2013, 40 (04) :451-457
[3]   Optical coherence tomography: feasibility for basic research and image-guided surgery of breast cancer [J].
Boppart, SA ;
Luo, W ;
Marks, DL ;
Singletary, KW .
BREAST CANCER RESEARCH AND TREATMENT, 2004, 84 (02) :85-97
[4]   EGFR family: Structure physiology signalling and therapeutic targets [J].
Burgess, Antony W. .
GROWTH FACTORS, 2008, 26 (05) :263-274
[5]  
Choy Garry, 2003, Mol Imaging, V2, P303, DOI 10.1162/153535003322750646
[6]  
Ciardiello F, 2002, EXPERT OPIN INV DRUG, V11, P755
[7]   Preclinical Comparison of Near-Infrared-Labeled Cetuximab and Panitumumab for Optical Imaging of Head and Neck Squamous Cell Carcinoma [J].
Day, Kristine E. ;
Sweeny, Larissa ;
Kulbersh, Brian ;
Zinn, Kurt R. ;
Rosenthal, Eben L. .
MOLECULAR IMAGING AND BIOLOGY, 2013, 15 (06) :722-729
[8]  
Fuss L., 2008, MOL ONCOL, V2
[9]   FluoSTIC: miniaturized fluorescence image-guided surgery system [J].
Gioux, Sylvain ;
Coutard, Jean-Guillaume ;
Berger, Michel ;
Grateau, Henri ;
Josserand, Veronique ;
Keramidas, Michelle ;
Righini, Christian ;
Coll, Jean-Luc ;
Dinten, Jean-Marc .
JOURNAL OF BIOMEDICAL OPTICS, 2012, 17 (10)
[10]   Image-Guided Surgery Using Invisible Near-Infrared Light: Fundamentals of Clinical Translation [J].
Gioux, Sylvain ;
Choi, Hak Soo ;
Frangioni, John V. .
MOLECULAR IMAGING, 2010, 9 (05) :237-255