PURPOSE: Cotinine has optimal characteristics as a hapten for pre-targeted radioimmunotherapy (PRIT). This study was performed to evaluate the applicability of cotinine/anti-cotinine antibody to PRIT. METHODS: We developed and prepared a tandem, single-chain, variable fragment Fc fusion protein [tandem single-chain variable fragment (scFv) Fc fusion protein] that is reactive to both human epidermal growth factor receptor 2 (Her2) and cotinine. Its simultaneous reactivity to Her2 and cotinine was tested in an enzyme-linked immunosorbent assay (ELISA) and two radioimmunoassays (RIA) employing Her2-coated RIA tubes and a Her2-overexpressing cell line. For in vivo imaging, mice bearing Her2-positive tumors were injected with a mixture of tandem scFv Fc fusion and (125)I-cotinine-conjugated histidine dipeptide ((125)I-cotinine peptide). After a delay, (125)I-cotinine peptide was injected again. RESULTS: ELISA and RIA results showed that tandem scFv Fc fusion protein successfully bound to both Her2 and cotinine. In single-photon emission computed tomography (SPECT), the complex of tandem scFv Fc fusion protein and (125)I-cotinine peptide was localized to Her2-positive tumor xenografts in mice 4 h after the first injection. Enhanced radioactivity at the site of the Her2-positive tumor lesion was monitored 1 h after the second injection. CONCLUSIONS: With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.
PURPOSE:Cotinine has optimal characteristics as a hapten for pre-targeted radioimmunotherapy (PRIT). This study was performed to evaluate the applicability of cotinine/anti-cotinine antibody to PRIT. METHODS: We developed and prepared a tandem, single-chain, variable fragment Fc fusion protein [tandem single-chain variable fragment (scFv) Fc fusion protein] that is reactive to both human epidermal growth factor receptor 2 (Her2) and cotinine. Its simultaneous reactivity to Her2 and cotinine was tested in an enzyme-linked immunosorbent assay (ELISA) and two radioimmunoassays (RIA) employing Her2-coated RIA tubes and a Her2-overexpressing cell line. For in vivo imaging, mice bearing Her2-positive tumors were injected with a mixture of tandem scFv Fc fusion and (125)I-cotinine-conjugated histidinedipeptide ((125)I-cotinine peptide). After a delay, (125)I-cotinine peptide was injected again. RESULTS: ELISA and RIA results showed that tandem scFv Fc fusion protein successfully bound to both Her2 and cotinine. In single-photon emission computed tomography (SPECT), the complex of tandem scFv Fc fusion protein and (125)I-cotinine peptide was localized to Her2-positive tumor xenografts in mice 4 h after the first injection. Enhanced radioactivity at the site of the Her2-positive tumor lesion was monitored 1 h after the second injection. CONCLUSIONS: With these findings, we conclude that the tandem scFv Fc fusion protein and cotinine hapten system have the potential to be applied in PRIT.
Authors: Tove Olafsen; Giselle J Tan; Chia-Wei Cheung; Paul J Yazaki; Jinha M Park; John E Shively; Lawrence E Williams; Andrew A Raubitschek; Michael F Press; Anna M Wu Journal: Protein Eng Des Sel Date: 2004-06-08 Impact factor: 1.650
Authors: Kelly Anderson; Zhihong Lai; Octerloney B McDonald; J Darren Stuart; Eldridge N Nartey; Mary Ann Hardwicke; Ken Newlander; Dashyant Dhanak; Jerry Adams; Denis Patrick; Robert A Copeland; Peter J Tummino; Jingsong Yang Journal: Biochem J Date: 2009-05-13 Impact factor: 3.857
Authors: Sarah M Cheal; Hong Xu; Hong-Fen Guo; Mitesh Patel; Blesida Punzalan; Edward K Fung; Sang-Gyu Lee; Meghan Bell; Manisha Singh; Achim A Jungbluth; Pat B Zanzonico; Alessandra Piersigilli; Steven M Larson; Nai-Kong V Cheung Journal: Theranostics Date: 2018-10-06 Impact factor: 11.556