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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: UNLABELLED, METHODS, RESULTS. Meshes: Aged, Animals, Antibodies, Monoclonal, Humanized, Autoradiography, Colorectal Neoplasms, Female, Humans, Iodine Radioisotopes, Male, Membrane Glycoproteins, Middle Aged, Multimodal Imaging, Positron-Emission Tomography, Protein Transport, Tomography, X-Ray Computed.
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Is 124I-huA33 antibody uptake driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET? Context: The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients. Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide (124)I ((124)I-huA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination. PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of (124)I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ~0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ~0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%.
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The in vivo biodistribution of (124)I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions. Final Decision: yes