⁶⁶Ga-Labeled PEGylated nano-graphene oxide (GO) covalently linked to NOTA-conjugated anti-CD105 (endoglin) chimeric monoclonal antibody TRC105

The CD105 antigen (endoglin) is a hypoxia-inducible, 180-kDa, disulfide-linked, homodimeric transmembrane glycoprotein that is a co-receptor for the transforming growth factor β (TGF-β) (1). Both CD105 and TGF-β are expressed at low levels in resting endothelial cells, but they are overexpressed in cancerous lesions and play a significantly proangiogenic role in remodeling the vasculature of malignant tumors (2). It has been shown that the levels of CD105 in endothelial tissues correlate well with the degree of cell proliferation and that the antigen is a suitable biomarker to quantify tumor angiogenesis and can be used to determine the prognostic outcome for cancer patients (3). The biological activity of CD105 has been discussed in detail by Seon et al. (4). Investigators have demonstrated that immunotoxins and radioimmunoconjugates generated with anti-CD105 monoclonal antibodies (mAbs) can inhibit angiogenesis and prevent the growth and metastasis of cancerous tumors (4). For translation to the clinic, a human/mouse chimeric anti-CD105 mAb (designated c-SNj6 or TRC105) was generated and shown to have suitable pharmacokinetic, toxicological, and immunogenicity characteristics for use in non-human primates (5). Currently, a clinical trial is in progress to evaluate the use of TRC105 for the treatment of metastatic breast cancer.

TRC105 has been labeled with ⁶⁴Cu (6) and ⁸⁹Zr (7), respectively, and has been reported to detect the expression of CD105 with positron emission tomography (PET) imaging in xenograft tumors in mice. In another study, TRC105 was conjugated to IRDye 800CW, a near-infrared fluorescent (NIRF) dye, and the expression of CD105 in tumors was visualized with NIRF imaging (8). TRC105 has also been conjugated with ⁶⁴Cu and IRDye 800CW to develop a dual-modality (PET/NIRF) imaging agent that can be used to detect murine breast cancer 4T1 cell tumors in mice (9). Recently, TRC105 was conjugated to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and labeled with ⁶⁶Ga, and the radioimmunoconjugate was shown to be suitable to visualize the expression of CD105 with PET in 4T1 cell tumors in mice (10).

Investigators have recently become interested in the use of PEGylated graphene oxide (GO; to read about the physical and chemical properties of graphene, see Feng and Liu (11)), a carbon-based material, in biomedical applications such as drug delivery (12), cancer therapy (13), and preclinical in vivo imaging and ablation of tumors in mice (14). Hong et al. used PET to evaluate ⁶⁶Ga-labeled PEGylated nano-GO covalently linked to NOTA-conjugated TRC105 ([⁶⁶Ga]-NOTA-GO-TRC105) to visualize and target tumors that express the CD105 antigen in mice (15).