Zr-Labeled -isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS)–conjugated panitumumab, a fully human monoclonal antibody directed against the extracellular domain III of the epidermal growth factor receptor

Panitumumab is a fully human anti-epidermal factor receptor 1 (HER1) monoclonal antibody (mAb) that has been approved by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancers that express the EGFR and are unresponsive to chemotherapy (1). This mAb has a very high affinity for the extracellular domain III of the HER1. The mode of action of panitumumab has been illustrated by Dubois and Cohen (1), and the general characteristics of this mAb have been described by Argiles et al. (2). The fully human mAb is well tolerated by individuals, slows disease progression, and improves the progression-free survival of patients (3). Therefore, In-labeled panitumumab was evaluated for the noninvasive detection of HER1-positive tumors in an effort to screen for patients who would benefit most from radioimmunotherapy with this mAb after labeling it with a suitable high-energy radionuclide (3). Cu-Labeled panitumumab has been used with positron emission tomography (PET) for the detection of head and neck squamous cell carcinoma xenograft tumors (these tumors express high levels of HER1) in mice, and it has been shown that only low levels of the labeled mAb accumulated in the lesions (4). The low uptake of the radiolabeled mAb by the tumors is attributed to poor vascular permeability of the lesions. Immunohistochemistry is the method of choice to quantify expression of the HER family of receptors in cancerous lesions, but results obtained with this technique do not establish a clear correlation between the response to anti-HER1 immunotherapy and the level of HER1 in the cancerous lesions (5). In other studies, Y-labeled panitumumab ([Y]-panitumumab) was used with PET to detect HER1-positive tumors in mice (6). It has also been shown that [Y]-panitumumab is superior to [Y]-cetuximab for determination of the HER1 status of malignant mesothelioma in mice (7). However, Cu and Y have half-lives of 12.7 h and 14.7 h, respectively, which may limit the imaging and quantification of tumors that express the HER1 beyond 3 days postinjection (p.i.) (8). Nayak et al. proposed that Zr would be a more suitable radionuclide than either Cu or Y to detect or quantify HER1 in tumors with PET because Zr has a half-life of 78.4 h and can be followed in the clinic for more than one week (8). Moreover, Zr-labeled trastuzumab was used successfully with PET to visualize and quantify HER2-positive metastatic breast cancer lesions and has been shown to produce better quality high spatial resolution images compared with In-labeled trastuzumab (9). Nayak et al. studied the biodistribution of Zr-labeled panitumumab ([Zr]-panitumumab) in mice bearing xenograft LS-174T cell tumors (human colorectal adenocarcinoma cells that express the HER1) and evaluated its utility to visualize HER1-positive tumors with PET in different animal models of metastatic cancer (8).