Visualizing Head and Neck Tumors in Vivo Using Near-Infrared Fluorescent Transferrin Conjugate

Abstract

Transferrin receptor (TfR) is overexpressed in human head and neck squamous cell carcinomas (HNSCCs). This study was carried out to investigate the feasibility of imaging HNSCC by targeting TfR using near-infrared fluorescent transferrin conjugate (TfNIR). Western blot analysis of four HNSCC cell lines revealed overexpression of TfR in all four lines compared with that in normal keratinocytes (OKFL). Immunocytochemistry further confirmed the expression of TfR and endocytosis of TfNIR in JHU-013 culture cells. Following intravenous administration of TfNIR (200 microL, 0.625 microg/microL), fluorescent signal was preferentially accumulated in JHU-013 tumor xenografts grown in the lower back (n=14) and oral base tissues (n=4) of nude mice. The signal in tumors was clearly detectable as early as 10 minutes and reached the maximum at 90 to 120 minutes postinjection. The background showed an increase, followed by a decrease at a much faster pace than tumor signal. A high fluorescent ratio of the tumor to muscle was obtained (from 1.42 to 4.15 among tumors), usually achieved within 6 hours, and correlated with the tumor size (r=.74, p=.002). Our results indicate that TfR is a promising target and that Tf(NIR)-based optical imaging is potentially useful for noninvasive detection of early HNSCC in the clinic.

A Systems Biology Approach to Iron Metabolism

“…Links between excess iron and cancer are also suggested by the efficacy of dietary iron deprivation [77] and iron chelators [78] in cancer therapy. In the early 1980’s it was observed that levels of transferrin receptor 1 (TfR1) are elevated in cancer, and use of TfR1 as a targeting ligand in the design of anti-cancer drugs was proposed [79,80]. …”

Image guided surgery in the management of head and neck cancer

“…A maximum signal intensity of the tumors was detected between 90 and 120 min after the injection and a high fluorescent ratio of tumor to muscle was obtained. [80]. Keereweer et al injected tumor-specific near-infrared fluorescence agents targeting glucose transporter system (CW800 2-DG) in mice with tongue tumors and cervical lymphadenopathy.…”

“…This peptide has been conjugated to multiple fluorophores or coupled with quantum dots to visualize avb3 integrin positive head and neck squamous cell carcinoma [75][76][77][78][79]. Transferrin receptor (TfR) is also appreciated to overexpress in the head and neck cancer and often associated with poor prognosis [80]. An in vivo study was conducted to determine the feasibility of targeting TfR using NIR fluorescent transferrin conjugate.…”

Progress in Molecular Imaging in Endoscopy and Endomicroscopy for Cancer Imaging

“…TfR antibody was labeled with Alexa-488. TfRNIR was injected into immunodeficient mice bearing HNSCC via tail vein, and animals were imaged using IVIS every 10–30 min up to at least 6 h [ 61 . The results indicated a potential use of anti-CD147 and TfR antibody for noninvasive head and neck tumor imaging.…”