Tc-Arcitumomab

[PubMed] Tc-Arcitumomab (Tc-IMMU-4), which is formed by the conjugation of Tc with a murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) Fab´ fragment, can be used for imaging CEA-expressing cancers (1). It was approved by the United States Food and Drug Administration (FDA) in 1999 as a diagnostic aid, in conjunction with standard diagnostic evaluations, for detection of the presence, location, and extent of recurrent and/or metastatic colorectal carcinoma involving the liver, extrahepatic abdomen, and pelvis in patients with a histologically confirmed diagnosis of colorectal carcinoma (2). However, it is no longer marketed in the United States. Tc-IMMU-4 is not indicated for the differential diagnosis of suspected colorectal carcinoma or as a screening tool for colorectal cancer, nor is it intended for readministration or for assessment of response to treatment. CEA was first identified from extracts of human adenocarcinoma of the colon (3). It is a β-glycoprotein, and its predominant expression on the cell surface is increased in a variety of carcinomas, particularly of the gastrointestinal tract, as well as in fetal gastrointestinal tissues and in certain inflammatory states, such as inflammatory bowel disease (1, 4). CEA, which exhibits extensive heterogeneity in its physicochemical and immunologic properties (3, 5), has a molecular weight of 200 kDa, and can be shed and detected in the serum (5). It has been used as a serum marker for monitoring disease status in patients who have various CEA- secreting tumors (gastrointestinal, lung, medullary, thyroid, uterine, ovarian, and bladder carcinomas). Other cross-reactive, but genetically distinct, CEA variants have been identified, including nonspecific cross-reactive antigen (NCA) and meconium antigen (MA) (2). Radiolabeled MAbs have been developed for both the diagnosis and treatment of tumors (4). IMMU-4 was developed from the anti-CEA NP-4 MAb (2, 5, 6). NP-4, a murine IgG MAb, binds only CEA and does not appear to cross-react with NCA or MA. IMMU-4 is obtained from NP-4 in the form of a 50-kDa monovalent Fab´ fragment, by pepsin digestion and is devoid of the immunogenic Fc portion (7). This improves the imaging pharmacokinetics of IMMU-4 by allowing faster clearance from the blood pool and other soft tissues, reducing liver metabolism, and improving the tumor/background ratio. Being a smaller molecule, the Fab´ fragment also minimizes induction of human anti-mouse antibodies (HAMAs) in patients. MAbs can be labeled with Tc by direct or indirect labeling. Direct labeling involves reduction of Tc pertechnetate and nonspecific binding of the reduced Tc to donor atoms, namely, thiol, amide, amino, and carboxylate (8). Indirect labeling uses a bifunctional chelating agent, which can be more binding site specific on the MAb molecule. IMMU-4 has also been labeled with radioactive iodine (9). In the FDA-approved product, IMMU-4 is directly labeled with Tc by use of a reducing agent. The IMMU-4 MAb in commercial preparations is produced in murine ascites fluid and is supplied as a lyophilized formulation that contains 1.25 mg of IMMU-4.