The Experts below are selected from a list of 4995 Experts worldwide ranked by ideXlab platform
Robert M Sharkey - One of the best experts on this subject based on the ideXlab platform.
-
pretargeted molecular imaging and radioimmunotherapy
Theranostics, 2012Co-Authors: David M Goldenberg, Chienhsing Chang, Edmund A Rossi, J William, Robert M SharkeyAbstract:Pretargeting is a multi-step process that first has an unlabeled bispecific Antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-Hapten Antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-Hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Winette T A Van Der GraafAbstract: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.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Annemarie EekAbstract:(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.
David M Goldenberg - One of the best experts on this subject based on the ideXlab platform.
-
pretargeted molecular imaging and radioimmunotherapy
Theranostics, 2012Co-Authors: David M Goldenberg, Chienhsing Chang, Edmund A Rossi, J William, Robert M SharkeyAbstract:Pretargeting is a multi-step process that first has an unlabeled bispecific Antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-Hapten Antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-Hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Winette T A Van Der GraafAbstract: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.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Annemarie EekAbstract:(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.
Barry W Edwards - One of the best experts on this subject based on the ideXlab platform.
-
discovery of Hapten specific scfv from a phage display library and applications for her2 positive tumor imaging
Bioconjugate Chemistry, 2014Co-Authors: Hyeyeong Kim, Xiaolei Wang, Brendon Wahlberg, Barry W EdwardsAbstract:In this study, an anti-Hapten Antibody (single chain Fv, scFv) against a Hapten probe was developed as a unique reporter system for molecular imaging or therapy. The Hapten peptide (histamine-succinyl-GSYK, Him) was synthesized for phage displayed scFv affinity selection and for conjugation with cypate (Cy-Him) for in vivo near-infrared (NIR) optical imaging. Hapten-specific scFvs were affinity selected from the human single fold phage display scFv libraries (Tomlinson I + J) with high specificity and affinity. Utilizing HER2 targeting as a model system, the highest affinity scFv (clone J42) was recombinantly fused to an anti-HER2 affibody (scFv-L-Aff) with no loss of affinity of either protein. The functionality of the Hapten-scFv reporter system was tested in vitro with a HER2-positive human breast cancer cell line, SK-BR3, and in vivo with SK-BR3 xenografts. ScFv-L-Aff mediated the binding of the Hapten to HER2 on SK-BR3 cells and from tissue from the SK-BR3 xenograft; however, scFv-L-Aff did not media...
-
discovery of Hapten specific scfv from a phage display library and applications for her2 positive tumor imaging
Bioconjugate Chemistry, 2014Co-Authors: Hyeyeong Kim, Xiaolei Wang, Brendon Wahlberg, Barry W EdwardsAbstract:In this study, an anti-Hapten Antibody (single chain Fv, scFv) against a Hapten probe was developed as a unique reporter system for molecular imaging or therapy. The Hapten peptide (histamine-succinyl-GSYK, Him) was synthesized for phage displayed scFv affinity selection and for conjugation with cypate (Cy-Him) for in vivo near-infrared (NIR) optical imaging. Hapten-specific scFvs were affinity selected from the human single fold phage display scFv libraries (Tomlinson I + J) with high specificity and affinity. Utilizing HER2 targeting as a model system, the highest affinity scFv (clone J42) was recombinantly fused to an anti-HER2 affibody (scFv-L-Aff) with no loss of affinity of either protein. The functionality of the Hapten-scFv reporter system was tested in vitro with a HER2-positive human breast cancer cell line, SK-BR3, and in vivo with SK-BR3 xenografts. ScFv-L-Aff mediated the binding of the Hapten to HER2 on SK-BR3 cells and from tissue from the SK-BR3 xenograft; however, scFv-L-Aff did not mediate uptake of the Hapten in the SK-BR3 xenografted tumors, presumably due to rapid internalization of the HER2/scFv-L-Aff complex. Our results suggest that this Hapten-peptide and anti-Hapten scFv can be a universal reporter system in a wide range of imaging and therapeutic applications.
Edmund A Rossi - One of the best experts on this subject based on the ideXlab platform.
-
pretargeted molecular imaging and radioimmunotherapy
Theranostics, 2012Co-Authors: David M Goldenberg, Chienhsing Chang, Edmund A Rossi, J William, Robert M SharkeyAbstract:Pretargeting is a multi-step process that first has an unlabeled bispecific Antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-Hapten Antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-Hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Winette T A Van Der GraafAbstract: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.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Annemarie EekAbstract:(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.
Chienhsing Chang - One of the best experts on this subject based on the ideXlab platform.
-
pretargeted molecular imaging and radioimmunotherapy
Theranostics, 2012Co-Authors: David M Goldenberg, Chienhsing Chang, Edmund A Rossi, J William, Robert M SharkeyAbstract:Pretargeting is a multi-step process that first has an unlabeled bispecific Antibody (bsMAb) localize within a tumor by virtue of its anti-tumor binding site(s) before administering a small, fast-clearing radiolabeled compound that then attaches to the other portion of the bsMAb. The compound's rapid clearance significantly reduces radiation exposure outside of the tumor and its small size permits speedy delivery to the tumor, creating excellent tumor/nontumor ratios in less than 1 hour. Haptens that bind to an anti-Hapten Antibody, biotin that binds to streptavidin, or an oligonucleotide binding to a complementary oligonucleotide sequence have all been radiolabeled for use by pretargeting. This review will focus on a highly flexible anti-Hapten bsMAb platform that has been used to target a variety of radionuclides to image (SPECT and PET) as well as treat tumors.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Winette T A Van Der GraafAbstract: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.
-
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
Molecular Cancer Therapeutics, 2010Co-Authors: Rafke Schoffelen, David M Goldenberg, Chienhsing Chang, Edmund A Rossi, Robert M Sharkey, Gerben M Franssen, William J Mcbride, Peter Laverman, Jonathan A Disselhorst, Annemarie EekAbstract:(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.
