PURPOSE: Improved bifunctional chelates (BFCs) are needed to facilitate efficient (64)Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with (64)Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). METHODS: The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. (64)Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. RESULTS: (64)Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of (64)Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that (64)Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the (64)Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the (64)Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. CONCLUSION: The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior (64)Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, (64)Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than the analogous (64)Cu-DOTA antibody conjugates.
PURPOSE: Improved bifunctional chelates (BFCs) are needed to facilitate efficient (64)Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with (64)Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). METHODS: The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. (64)Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. RESULTS: (64)Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of (64)Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that (64)Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the (64)Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the (64)Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor. CONCLUSION: The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior (64)Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, (64)Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than the analogous (64)Cu-DOTA antibody conjugates.
Authors: Desiree M Crow; Lawrence Williams; David Colcher; Jeffrey Y C Wong; Andrew Raubitschek; John E Shively Journal: Bioconjug Chem Date: 2005 Sep-Oct Impact factor: 4.774
Authors: Stephan D Voss; Suzanne V Smith; Nadine DiBartolo; Lacey J McIntosh; Erika M Cyr; Ali A Bonab; Jason L J Dearling; Edward A Carter; Alan J Fischman; S Ted Treves; Stephen D Gillies; Alan M Sargeson; James S Huston; Alan B Packard Journal: Proc Natl Acad Sci U S A Date: 2007-10-22 Impact factor: 11.205
Authors: Sara Ahlgren; Helena Wållberg; Thuy A Tran; Charles Widström; Magnus Hjertman; Lars Abrahmsén; Dietmar Berndorff; Ludger M Dinkelborg; John E Cyr; Joachim Feldwisch; Anna Orlova; Vladimir Tolmachev Journal: J Nucl Med Date: 2009-04-16 Impact factor: 10.057
Authors: Maggie S Cooper; Michelle T Ma; Kavitha Sunassee; Karen P Shaw; Jennifer D Williams; Rowena L Paul; Paul S Donnelly; Philip J Blower Journal: Bioconjug Chem Date: 2012-04-13 Impact factor: 4.774
Authors: William M Rockey; Ling Huang; Kyle C Kloepping; Nicholas J Baumhover; Paloma H Giangrande; Michael K Schultz Journal: Bioorg Med Chem Date: 2011-05-14 Impact factor: 3.641
Authors: Gwendolyn A Bailey; Eric W Price; Brian M Zeglis; Cara L Ferreira; Eszter Boros; Michael J Lacasse; Brian O Patrick; Jason S Lewis; Michael J Adam; Chris Orvig Journal: Inorg Chem Date: 2012-10-29 Impact factor: 5.165
Authors: Eduardo Aluicio-Sarduy; Paul A Ellison; Todd E Barnhart; Weibo Cai; Robert Jerry Nickles; Jonathan W Engle Journal: J Labelled Comp Radiopharm Date: 2018-03-12 Impact factor: 1.921
Authors: Jiyun Shi; Tracy W B Liu; Juan Chen; David Green; David Jaffray; Brian C Wilson; Fan Wang; Gang Zheng Journal: Theranostics Date: 2011-09-15 Impact factor: 11.556
Authors: Artor Niccoli Asabella; Giuseppe Lucio Cascini; Corinna Altini; Domenico Paparella; Antonio Notaristefano; Giuseppe Rubini Journal: Biomed Res Int Date: 2014-05-07 Impact factor: 3.411