Head and neck cancer accounts for more than 600,000 deaths per year, worldwide. The prognosis for this disease is poor and the 5-year survival rate is only 50%. Targeted agents have emerged as therapeutic options in combination with radiation therapy and/or chemotherapy. Prominent among them is an epidermal growth factor receptor (EGFR)-inhibiting monoclonal antibody, Cetuximab. While EGFR is overexpressed in head and neck tumor cell membranes, diagnostic tools to monitor the uptake of the targeted agent are currently lacking. We aimed to develop a lipid based probe bearing anti-EGFR antibodies and gadolinium (Gd), a positive (image-brightening) contrast agent for magnetic resonance imaging (MRI) to monitor the tissue uptake of Cetuximab in vitro and evaluate the effects on xenograft mice in vivo. Here, we report on a simple self-assembly-based strategy to synthesize such liposomal probes as well as solid lipid nanoprobes (SLN), which involve combining biocompatible phospholipids, a chelated-Gd lipid, and a biotinylated lipid, followed by attachment of biotinylated antibodies using avidin as linker. Our results demonstrate that these probes preferentially bind to head and neck cancer cells compared to low-EGFR-expressing cells. Moreover, the EGFR-specific targeting resulted in a high MR contrast localized around the targeted cells. In vivo studies indicate that the probes are retained at the tumor site in nude mice. Such probes can potentially provide targeting specificity during the treatment regimen and allow physicians to adjust therapeutic strategies.

Multifunctional nanoprobes detectable by MRI for monitoring cancer therapy

246th National Meeting (2013)

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