Details

Autor(en) / Beteiligte

• Bhattacharyya, Sibaprasad
• Patel, Nimit L
• Wei, Ling
• Riffle, Lisa A
• Kalen, Joseph D
• Hill, G. Craig
• Jacobs, Paula M
• Zinn, Kurt R
• Rosenthal, Eben

Titel

Synthesis and biological evaluation of panitumumab-IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancersElectronic supplementary information (ESI) available: 2D and 3D in vivo images of mice xenografts at various time points are shown in Fig. S1 and S2. See DOI: 10.1039/c4md00116h

Erscheinungsjahr

2014-08

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 ( R 2 = 0.91) between EGFR-expression level and tumor uptake. Uptake of panitumumab labeled with IR-Dye or [ 89 Zr] 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. The optimized synthesis and biological evaluation of panitumumab-IRDye conjugate for its potential use as an intraoperative optical imaging agent are described.