Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a ⁶⁸Ga- and ¹⁸F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts

Abstract

¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting several cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small (∼1451 Da) hapten peptide with ⁶⁸Ga or ¹⁸F to compare their specificity with ¹⁸F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic antigen (CEA; CEACAM5)–expressing LS174T human colonic tumors and a CEA-negative tumor, or an inflammation was induced in thigh muscle. A bispecific monoclonal anti-CEA × anti-hapten antibody was given to mice, and 16 hours later, 5 MBq of ⁶⁸Ga- or ¹⁸F-labeled hapten peptides were administered intravenously. Within 1 hour, tissues showed high and specific targeting of ⁶⁸Ga-IMP-288, with 10.7 ± 3.6% ID/g uptake in the tumor and very low uptake in normal tissues (e.g., tumor-to-blood ratio of 69.9 ± 32.3), in a CEA-negative tumor (0.35 ± 0.35% ID/g), and inflamed muscle (0.72 ± 0.20% ID/g). ¹⁸F-FDG localized efficiently in the tumor (7.42 ± 0.20% ID/g) but also in the inflamed muscle (4.07 ± 1.13% ID/g) and in several normal tissues; thus, pretargeted ⁶⁸Ga-IMP-288 provided better specificity and sensitivity. Positron emission tomography (PET)/computed tomography images reinforced the improved specificity of the pretargeting method. ¹⁸F-labeled IMP-449 distributed similarly in the tumor and normal tissues as the ⁶⁸Ga-labeled IMP-288, indicating that either radiolabeled hapten peptide could be used. Thus, pretargeted immuno-PET does exceptionally well with short-lived radionuclides and is a highly sensitive procedure that is more specific than ¹⁸F-FDG-PET. Mol Cancer Ther; 9(4); 1019–27. ©2010 AACR.