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

R. Schoffelen, R. Sharkey, D. Goldenberg, G. Franssen, W. McBride, E. Rossi, C. Chang, P. Laverman, J. Disselhorst, A. Eek, W. van der Graaf, W. Oyen and O. Boerman

Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Apr, 2010



(18)F-Fluorodeoxyglucose ((18)F-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 ( approximately 1451 Da) hapten peptide with (68)Ga or (18)F to compare their specificity with (18)F-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 x anti-hapten antibody was given to mice, and 16 hours later, 5 MBq of (68)Ga- or (18)F-labeled hapten peptides were administered intravenously. Within 1 hour, tissues showed high and specific targeting of (68)Ga-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). (18)F-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 (68)Ga-IMP-288 provided better specificity and sensitivity. Positron emission tomography (PET)/computed tomography images reinforced the improved specificity of the pretargeting method. (18)F-labeled IMP-449 distributed similarly in the tumor and normal tissues as the (68)Ga-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 (18)F-FDG-PET. Mol Cancer Ther; 9(4); 1019-27. (c)2010 AACR.