PURPOSE: To prospectively determine if a bispecific monoclonal antibody (MoAb) pretargeting method with a radiolabeled hapten peptide can depict small (<0.3 mm in diameter) microdisseminated human colon cancer colonies in the lungs of nude mice. MATERIALS AND METHODS: Animal studies were approved in advance by animal care and use committees. Animals injected intravenously with a human colon cancer cell line to establish microdisseminated colonies in the lungs were pretargeted with TF2--a recombinant, humanized, anti-carcinoembryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) bispecific MoAb; 21 hours later, a radiolabeled HSG peptide was given. Imaging and necropsy data for tumor-bearing animals given the anti-CEA bispecific MoAb (n = 38, all studies) were compared with those of animals given fluorine 18 ((18)F) fluorodeoxyglucose (FDG) (n = 15, all studies), peptide alone (n = 20, all studies), or an irrelevant anti-CD22 bispecific MoAb (n = 12, all studies). Uptake of these agents in the lungs of non-tumor-bearing animals enabled assessment of specificity (n = 15, 4, and 6 for TF2 pretarget, hapten peptide alone, and (18)F-FDG, respectively). RESULTS: TF2-pretargeting helped localize tumors in the lungs within 1.5 hours of the radiolabeled HSG peptide injection, while the peptide alone, irrelevant bispecific MoAb pretargeted peptide, and (18)F-FDG failed. Necropsy data indicated that the signal in tumor-bearing lungs was five times higher than in blood within 1.5 hours, increasing to 50 times higher by 24 hours. Peptide uptake in tumor-bearing lungs pretargeted with TF2 was nine times higher than in non-tumor-bearing lungs, while it was only 1.5-fold higher with (18)F-FDG or the peptide alone. Micro-positron emission tomographic (PET) images showed discrete uptake in individual metastatic tumor colonies; autoradiographic data demonstrated selective targeting within the lungs, including metastases less than 0.3 mm in diameter. CONCLUSION: Bispecific antibody pretargeting is highly specific for imaging micrometastatic disease and may thus provide a complementary method to (18)F-FDG at clinical examination. (c) RSNA, 2008.
PURPOSE: To prospectively determine if a bispecific monoclonal antibody (MoAb) pretargeting method with a radiolabeled hapten peptide can depict small (<0.3 mm in diameter) microdisseminated humancolon cancer colonies in the lungs of nude mice. MATERIALS AND METHODS: Animal studies were approved in advance by animal care and use committees. Animals injected intravenously with a humancolon cancer cell line to establish microdisseminated colonies in the lungs were pretargeted with TF2--a recombinant, humanized, anti-carcinoembryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) bispecific MoAb; 21 hours later, a radiolabeled HSG peptide was given. Imaging and necropsy data for tumor-bearing animals given the anti-CEA bispecific MoAb (n = 38, all studies) were compared with those of animals given fluorine 18 ((18)F) fluorodeoxyglucose (FDG) (n = 15, all studies), peptide alone (n = 20, all studies), or an irrelevant anti-CD22 bispecific MoAb (n = 12, all studies). Uptake of these agents in the lungs of non-tumor-bearing animals enabled assessment of specificity (n = 15, 4, and 6 for TF2 pretarget, hapten peptide alone, and (18)F-FDG, respectively). RESULTS: TF2-pretargeting helped localize tumors in the lungs within 1.5 hours of the radiolabeled HSG peptide injection, while the peptide alone, irrelevant bispecific MoAb pretargeted peptide, and (18)F-FDG failed. Necropsy data indicated that the signal in tumor-bearing lungs was five times higher than in blood within 1.5 hours, increasing to 50 times higher by 24 hours. Peptide uptake in tumor-bearing lungs pretargeted with TF2 was nine times higher than in non-tumor-bearing lungs, while it was only 1.5-fold higher with (18)F-FDG or the peptide alone. Micro-positron emission tomographic (PET) images showed discrete uptake in individual metastatic tumor colonies; autoradiographic data demonstrated selective targeting within the lungs, including metastases less than 0.3 mm in diameter. CONCLUSION: Bispecific antibody pretargeting is highly specific for imaging micrometastatic disease and may thus provide a complementary method to (18)F-FDG at clinical examination. (c) RSNA, 2008.
Authors: William J McBride; Christopher A D'Souza; Habibe Karacay; Robert M Sharkey; David M Goldenberg Journal: Bioconjug Chem Date: 2012-02-10 Impact factor: 4.774
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Authors: Rafke Schoffelen; Robert M Sharkey; David M Goldenberg; Gerben Franssen; William J McBride; Edmund A Rossi; Chien-Hsing Chang; Peter Laverman; Jonathan A Disselhorst; Annemarie Eek; Winette T A van der Graaf; Wim J G Oyen; Otto C Boerman Journal: Mol Cancer Ther Date: 2010-03-30 Impact factor: 6.261
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