- Open Access
The effect of near-infrared fluorescence conjugation on the anti-cancer potential of cetuximab
Laboratory Animal Research volume 34, pages 30–36 (2018)
This study investigated the anti-cancer potential of a near-infrared fluorescence (NIRF) molecule conjugated with Cetuximab (Cetuximab-NIRF) in six-week-old female BALB/c athymic (nu+/nu+) nude mice. A431 cells were cultured and injected into the animals to induce solid tumors. Paclitaxel (30 mg/kg body weight (BW)), Cetuximab (1 mg/kg BW), and Cetuximab-NIRF (0.25, 0.5 and 1.0 mg/kg BW) were intraperitoneally injected twice a week into the A431 cell xenografts of the nude mice. Changes in BW, tumor volume and weight, fat and lean mass, and diameter of the peri-tumoral blood vessel were determined after two weeks. Tumor volumes and weights were significantly decreased in the Cetuximab-NIRF (1 mg/kg BW) group compared with the control group (P<0.001). Lean mass and total body water content were also conspicuously reduced in the Cetuximab-NIRF (1 mg/kg BW) group compared with the vehicle control group. Peri-tumoral blood vessel diameters were very thin in the Cetuximab-NIRF groups compared with those of the paclitaxel group. These results indicate that the conjugation of Cetuximab with NIRF does not affect the anti-cancer potential of Cetuximab and NIRF can be used for molecular imaging in cancer treatments.
Arteaga CL. EGF receptor as a therapeutic target: patient selection and mechanisms of resistance to receptor-targeted drugs. J Clin Oncol 2003; 21(23 Suppl): 289s–291s.
Wheeler DL, Dunn EF, Harari PM. Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol 2010; 7(9): 493–507.
Peng D, Fan Z, Lu Y, DeBlasio T, Scher H, Mendelsohn J. Anti- epidermal growth factor receptor monoclonal antibody 225 up- regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145. Cancer Res 1996; 56(16): 3666–3669.
Fagin JA. The Jeremiah Metzger lecture: intelligent design of cancer therapy: trials and tribulations. Trans Am Clin Climatol Assoc 2007; 118: 253–261.
Perrotte P, Matsumoto T, Inoue K, Kuniyasu H, Eve BY, Hicklin DJ, Radinsky R, Dinney CPN. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999; 5(2): 257–265.
Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997; 151(6): 1523–1530.
Pepper C, Hoy T, Bentley DP. Bcl-2/Bax ratios in chronic lymphocytic leukaemia and their correlation with in vitro apoptosis and clinical resistance. Br J Cancer 1997; 76(7): 935–938.
Wu X, Fan Z, Masui H, Rosen N, Mendelsohn J. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J Clin Invest 1995; 95(4): 1897–1905.
Ciardiello F, Bianco R, Damiano V, De Lorenzo S, Pepe S, De Placido S, Fan Z, Mendelsohn J, Bianco AR, Tortora G. Antitumor activity of sequential treatment with topotecan and anti-epidermal growth factor receptor monoclonal antibody C225. Clin Cancer Res 1999; 5(4): 909–916.
Wild R, Fager K, Flefleh C, Kan D, Inigo I, Castaneda S, Luo FR, Camuso A, McGlinchey K, Rose WC. Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels. Mol Cancer Ther 2006; 5(1): 104–113.
Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004; 22(7): 1201–1208.
Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351(4): 337–345.
Resch-Genger U, Grabolle M, Cavaliere-Jaricot S, Nitschke R, Nann T. Quantum dots versus organic dyes as fluorescent labels. Nat Methods 2008; 5(9): 763–775.
Zhang J, Campbell RE, Ting AY, Tsien RY. Creating new fluorescent probes for cell biology. Nat Rev Mol Cell Biol 2002; 3(12): 906–918.
Waggoner A. Fluorescent labels for proteomics and genomics. Curr Opin Chem Biol 2006; 10(1): 62–66.
Cai W, Chen X. Multimodality molecular imaging of tumor angiogenesis. J Nucl Med 2008; 49(2 Suppl): 113S–128S.
Barrett T, Koyama Y, Hama Y, Ravizzini G, Shin IS, Jang BS, Paik CH, Urano Y, Choyke PL, Kobayashi H. In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies. Clin Cancer Res 2007; 13(22 Pt 1): 6639–6648.
Mendelsohn J. The epidermal growth factor receptor as a target for cancer therapy. Endocr Relat Cancer 2001; 8(1): 3–9.
Ma T, Liu H, Sun X, Gao L, Shi J, Zhao H, Jia B, Wang F, Liu Z. Serial in vivo imaging using a fluorescence probe allows identification of tumor early response to cetuximab immunotherapy. Mol Pharm 2015; 12(1): 10–17.
Weissleder R, Tung CH, Mahmood U, Bogdanov A Jr. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999; 17(4): 375–378.
Van Emburgh BO, Sartore-Bianchi A, Di Nicolantonio F, Siena S, Bardelli A. Acquired resistance to EGFR-targeted therapies in colorectal cancer. Mol Oncol 2014; 8(6): 1084–1094.
Wunder A, Tung CH, Müller-Ladner U, Weissleder R, Mahmood U. In vivo imaging of protease activity in arthritis: a novel approach for monitoring treatment response. Arthritis Rheum 2004; 50(8): 2459–2465.
Baselga J, Norton L, Masui H, Pandiella A, Coplan K, Miller WH Jr, Mendelsohn J. Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J Natl Cancer Inst 1993; 85(16): 1327–1333.
Fan Z, Baselga J, Masui H, Mendelsohn J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res 1993; 53(19): 4637–4642.
Mukherjee P, Bhattacharya R, Wang P, Wang L, Basu S, Nagy JA, Atala A, Mukhopadhyay D, Soker S. Antiangiogenic properties of gold nanoparticles. Clin Cancer Res 2005; 11(9): 3530–3534.
Takata M, Chikumi H, Miyake N, Adachi K, Kanamori Y, Yamasaki A, Igishi T, Burioka N, Nanba E, Shimizu E. Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity. Cancer Biol Ther 2012; 13(6): 369–378.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27–31.
Fonsatti E, Nicolay HJ, Altomonte M, Covre A, Maio M. Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumours. Cardiovasc Res 2010; 86(1): 12–19.
Yang Y, Zhang Y, Hong H, Liu G, Leigh BR, Cai W. In vivo near- infrared fluorescence imaging of CD105 expression during tumor angiogenesis. Eur J Nucl Med Mol Imaging 2011; 38(11): 2066–2076.
Bandyopadhyay D, Mandal M, Adam L, Mendelsohn J, Kumar R. Physical interaction between epidermal growth factor receptor and DNA-dependent protein kinase in mammalian cells. J Biol Chem 1998; 273(3): 1568–1573.
Tseng SH, Chou MY, Chu IM. Cetuximab-conjugated iron oxide nanoparticles for cancer imaging and therapy. Int J Nanomedicine 2015; 10: 3663–3685.
Conde J, Bao C, Cui D, Baptista PV, Tian F. Antibody-drug gold nanoantennas with Raman spectroscopic fingerprints for in vivo tumour theranostics. J Control Release 2014; 183: 87–93.
Rights and permissions
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Yun, J.Y., Hyun, BH., Nam, S.Y. et al. The effect of near-infrared fluorescence conjugation on the anti-cancer potential of cetuximab. Lab Anim Res 34, 30–36 (2018). https://doi.org/10.5625/lar.2018.34.1.30
- near-infrared fluorescence
- A431 cells