PT  - JOURNAL ARTICLE
AU  - Schoffelen, Rafke
AU  - Sharkey, Robert M.
AU  - Goldenberg, David M.
AU  - Franssen, Gerben
AU  - McBride, William J.
AU  - Rossi, Edmund A.
AU  - Chang, Chien-Hsing
AU  - Laverman, Peter
AU  - Disselhorst, Jonathan A.
AU  - Eek, Annemarie
AU  - van der Graaf, Winette T.A.
AU  - Oyen, Wim J.G.
AU  - Boerman, Otto C.
TI  - Pretargeted Immuno–Positron Emission Tomography Imaging of Carcinoembryonic Antigen–Expressing Tumors with a Bispecific Antibody and a <sup>68</sup>Ga- and <sup>18</sup>F-Labeled Hapten Peptide in Mice with Human Tumor Xenografts
AID  - 10.1158/1535-7163.MCT-09-0862
DP  - 2010 Apr 01
TA  - Molecular Cancer Therapeutics
PG  - 1019--1027
VI  - 9
IP  - 4
4099  - http://mct.aacrjournals.org/content/9/4/1019.short
4100  - http://mct.aacrjournals.org/content/9/4/1019.full
SO  - Mol Cancer Ther2010 Apr 01; 9
AB  - 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.©2010 American Association for Cancer Research.