Cetuximab-IRDye800CW (University Medical Center Groningen)

Cetuximab (Cet)-IRDye800CW, among other antibody-IRDye800CW conjugates, is a potentially effective tool for delineating tumor margins during fluorescence image-guided surgery (IGS). However, residual disease often leads to recurrence. Photodynamic therapy (PDT) following IGS is proposed as an approach to eliminate residual disease but suffers from a lack of molecular specificity for cancer cells. Antibody-targeted PDT offers a potential solution for this specificity problem. In this study, we show, for the first time, that Cet-IRDye800CW is capable of antibody-targeted PDT in vitro when the payload of dye molecules is increased from 2 (clinical version) to 11 per antibody. Cet-IRDye800CW (1:11) produces singlet oxygen, hydroxyl radicals, and peroxynitrite upon activation with 810 nm light. In vitro assays on FaDu head and neck cancer cells confirm that Cet-IRDye800CW (1:11) maintains cancer cell binding specificity and is capable of inducing up to ∼90% phototoxicity in FaDu cancer cells. The phototoxicity of Cet-IRDye800CW conjugates using 810 nm light follows a dye payload-dependent trend. Cet-IRDye800CW (1:11) is also found to be more phototoxic to FaDu cancer cells and less toxic in the dark than the approved chromophore indocyanine green, which can also act as a PDT agent. We propose that antibody-targeted PDT using high-payload Cet-IRDye800CW (1:11) could hold potential for eliminating residual disease postoperatively when using sustained illumination devices, such as fiber optic patches and implantable surgical bed balloon applicators. This approach could also potentially be applicable to a wide variety of resectable cancers that are amenable to IGS-PDT, using their respective approved full-length antibodies as a template for high-payload IRDye800CW conjugation.

Precise resection of hepatic carcinoma (HCC) remains challenging for cirrhotic patients. Cirrhosis not only effects intraoperative palpation, but can also cause severe false-positive problems to indocyanine green (ICG) fluorescence imaging. Herein, we report the application of a nano-scale probe IgG-IRDye800CW to achieve precise HCC resection from cirrhotic liver. A 66-year-old male patient with liver cancer received intravenous injection of IgG-IRDye800CW (10 mg) 6 days prior to surgery, and none adverse effects were observed. During the operation, the HCC lesion in the right liver lobe was specifically detected on the near-infrared window II (NIR-II) fluorescence images. The high-contrast NIR-II fluorescence delineated a clear margin to improve surgical precision. These clinical observations showed high safety and feasibility of applying IgG-IRDye800CW NIR-II fluorescence imaging to guide hepatic surgery and minimize hepatic function damage.