Radioiodinated anti-CEA monoclonal antibody NP-4 F(ab´) fragment

Radioiodinated anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) NP-4 F(ab´) fragment (I/I/I-NP-4 F(ab´)), which is formed by the conjugation of radioiodine with a murine anti-CEA MAb F(ab´) fragment, can be used for imaging and therapy of CEA-expressing cancers (1, 2). I has a relatively long physical half-life () of 60 days and a gamma energy that makes it suitable for imaging only in small animals. I has a physical half-life () of 8.02 days with a gamma energy that is high but acceptable for imaging. I, another radioiodine, has better physical properties for single-photon emission computed tomography (SPECT) and planar gamma imaging in humans. 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 (4, 5). CEA, which exhibits extensive heterogeneity in its physicochemical and immunologic properties (2, 3), has a molecular mass of 200 kDa and can be shed and detected in the serum (2). 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) (6). Radiolabeled MAbs have been developed for both the diagnosis and treatment of tumors (4). Primus et al. (2) studied the immunologic heterogeneity of CEA by use of four MAbs to differentiate the antigenic sites on colonic cancer CEA. They classified the MAbs into three general classes based on their reactivity with CEA, NCA, and MA. The class I antibody, NP-1, had high affinity for CEA and MA but low affinity for NCA. The class II antibodies, NP-2 and NP-3, had moderate affinities for CEA and MA. The class III antibody, NP-4, appeared to recognize determinants unique to CEA and had no affinity for NCA or MA. Because of this specificity, NP-4 MAb has been labeled with radionuclides for CEA tumor imaging and therapy (7). Intact NP-4 MAb can be covalently linked to I, I, or I by direct radioiodination with NaI, NaI, or NaI, using an appropriate oxidizing agent. Because of differences in their radiation physical properties, I can be used for both therapy and imaging, I is used only for imaging, and I is used mainly for studies. The pharmacokinetics of intact radiolabeled immunoglobulin G (IgG) in humans are characterized by high liver uptake and slow blood elimination. Therefore, the intact radiolabeled NP-4 MAb is generally not ideal for imaging. Smaller radiolabeled MAb fragments such as Fob or F(ab´) may have better imaging pharmacokinetics because they are rapidly excreted by the kidneys. Covell et al. (8) reported that the percentages of total body catabolism of an i.v.-administered I-labeled MAb and its fragments by the kidney were 1.7% (intact IgG), 50.3% (F(ab´)), and 73.4% (Fab´).