¹²⁴I-Labeled humanized CH2-domain-deleted anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody

Tumor-associated glycoprotein 72 (TAG-72) is a high molecular weight mucigenous protein that is found mainly in the extracellular matrix of neoplastic tumors (1). This glycoprotein is usually not expressed in normal tissues, but it is overexpressed in the tumors of several cancers, such as those of the colon and rectum (colorectal cancer), stomach, pancreas, ovaries, prostate, lung, breast, etc. Therefore, TAG-72 is considered to have a great deal of theranostic value (useful for the diagnosis and/or therapy of a disease) because it can be used for antigen-directed surgical resection of cancerous tumors with radiolabeled anti-TAG-72 monoclonal antibodies (mAb) (1). In addition, the detection or absence of TAG-72 expression in colorectal cancer tumors has been shown to have a prognostic value because individuals who had complete removal of tumors with surgery guided by mouse anti-TAG-72 mAb were shown to have a long-term survival advantage compared to patients who had incomplete removal of the lesions (2). In an effort to develop diagnostic agents that can be used for the rapid detection of tumors that overexpress TAG-72, investigators developed a ¹²⁵I-labeled complimentary determining region–grafted humanized C_H2-domain-deleted anti-TAG-72 mAb ([¹²⁵I]-HuCC49deltaC_H2) and showed that it can be used in preclinical (mouse model) and human clinical settings to detect xenograft colorectal cancer tumors positive for TAG-72 (3). In the human studies, the ¹²⁵I-labeled mAb was used in conjunction with a hand-held gamma detection probe that assisted the surgeon to precisely locate and resect the tumor, which resulted in improved prognosis for the patient (4).

However, the main limitation of using ¹²⁵I to develop a targeted tracer is that this radionuclide has a long half-life (~60 days) and is difficult to handle, store, and dispose from the hospital operating room (4). In addition, it is not the most suitable radionuclide for diagnostic imaging because it is a low-energy gamma emitter and generates low-quality images with scintigraphy. Therefore, as an alternative, investigators have used ¹²⁴I to produce various types of imaging probes (small molecules, proteins antibodies, etc.) because it has a half-life of ~4 days, emits β particles that yield superior images with positron emission tomography (PET), and is easier to handle, store, and dispose. On the basis of this information, Zou et al. labeled HuCC49deltaC_H2 with ¹²⁴I ([¹²⁴I]-HuCC49deltaC_H2) and in a preliminary study evaluated the ¹²⁴I-labeled mAb for the detection of LS174T colon adenocarcinoma cell xenograft tumors (that express high levels of TAG-72) with PET in nude mice (4).