期刊
MOLECULAR CANCER THERAPEUTICS
卷 9, 期 4, 页码 1019-1027出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-09-0862
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资金
- Immunomedics, Inc.
- IBC Pharmaceuticals, Inc.
- Dutch Cancer Society (Koningin Wilhelmina Fonds Kankerbestrijding) [KUN 2008-4038]
- National Institute of Biomedical Imaging and Bioengineering, NIH [1 R43 EB003751]
F-18-Fluorodeoxyglucose (F-18-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 (similar to 1451 Da) hapten peptide with Ga-68 or F-18 to compare their specificity with F-18-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 Ga-68-or F-18-labeled hapten peptides were administered intravenously. Within 1 hour, tissues showed high and specific targeting of Ga-68-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 Ga-68-IMP-288 provided better specificity and sensitivity. Positron emission tomography (PET)/computed tomography images reinforced the improved specificity of the pretargeting method. F-18-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 F-18-FDG-PET. Mol Cancer Ther; 9(4); 1019-27. (C) 2010 AACR.
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