Pretargeted ImmunoPET Imaging of CEA-expressing Tumors with a Bispecific Antibody and a 68Ga- and 18F-labeled Hapten-peptide in Mice with Human Tumor Xenografts

摘要

¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) is the most common molecular imaging agent in oncology, with a high sensitivity and specificity for detecting a number of cancers. Antibodies could enhance specificity; therefore, procedures were developed for radiolabeling a small (∼1.5 kD) hapten-peptide with ⁶⁸Ga or ¹⁸F to compare their specificity to ¹⁸F-FDG for detecting tumors using a pretargeting procedure. Mice were implanted with carcinoembryonic (CEA; CEACAM5)-expressing LS174T human colonic tumors, a CEA-negative tumor, or an inflammation was induced in thigh muscle. A bispecific monoclonal (bsMAb) anti-CEA × anti-hapten antibody was given to mice, and 16 h later, 5 MBq of ⁶⁸Ga- or ¹⁸F-labeled hapten-peptides were administered intravenously. Within 1 h, tissues showed high and specific targeting of the ⁶⁸Ga-IMP-288, with 10.7 ± 3.6% ID/g uptake in the tumor and very low uptake in normal tissues (e.g., tumor/blood 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 a number of normal tissues; thus, pretargeted ⁶⁸Ga-IMP-288 provided better specificity and sensitivity. PET/CT 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 immunoPET performs exceptionally well with short-lived radionuclides, and is a highly sensitive procedure that is more specific than ¹⁸F-FDG-PET.