p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging – ScienceOpen
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      p-Isothiocyanatobenzyl-desferrioxamine: a new bifunctional chelate for facile radiolabeling of monoclonal antibodies with zirconium-89 for immuno-PET imaging

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          Abstract

          Purpose

          Immuno-PET is an emerging imaging tool for the selection of high potential antibodies (mAbs) for imaging and therapy. The positron emitter zirconium-89 ( 89Zr) has attractive characteristics for immuno-PET with intact mAbs. Previously, we have described a multi-step procedure for stable coupling of 89Zr to mAbs via the bifunctional chelate (BFC) tetrafluorophenol- N-succinyldesferal (TFP- N-sucDf). To enable widespread use of 89Zr-immuno-PET, we now introduce the novel BFC p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) and compare its performance in 89Zr-immuno-PET with the reference BFC TFP- N-sucDf.

          Methods

          Three mAbs were premodified with Df-Bz-NCS and labeled with 89Zr at different pHs to assess the reaction kinetics and robustness of the radiolabeling. Stability of both 89Zr-Df-Bz-NCS- and 89Zr- N-sucDf-conjugates was evaluated in different buffers and human serum. Comparative biodistribution and PET studies in tumor-bearing mice were undertaken.

          Results

          The selected conjugation conditions resulted in a chelate:mAb substitution ratio of about 1.5:1. Under optimal radiolabeling conditions (pH between 6.8–7.2), the radiochemical yield was >85% after 60 min incubation at room temperature, resulting in radioimmunoconjugates with preserved integrity and immunoreactivity. The new radioimmunoconjugate was very stable in serum for up to 7 days at 37°C, with <5% 89Zr release, and was equally stable compared to the reference conjugate when stored in the appropriate buffer at 4°C. In biodistribution and imaging experiments, the novel and the reference radioimmunoconjugates showed high and similar accumulation in tumors in nude mice.

          Conclusions

          The novel Df-Bz-NCS BFC allows efficient and easy preparation of optimally performing 89Zr-labeled mAbs, facilitating further exploration of 89Zr-immuno-PET as an imaging tool.

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          Most cited references26

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          Amide's a Medical Image Data Examiner (AMIDE) has been developed as a user-friendly, open-source software tool for displaying and analyzing multimodality volumetric medical images. Central to the package's abilities to simultaneously display multiple data sets (e.g., PET, CT, MRI) and regions of interest is the on-demand data reslicing implemented within the program. Data sets can be freely shifted, rotated, viewed, and analyzed with the program automatically handling interpolation as needed from the original data. Validation has been performed by comparing the output of AMIDE with that of several existing software packages. AMIDE runs on UNIX, Macintosh OS X, and Microsoft Windows platforms, and it is freely available with source code under the terms of the GNU General Public License.
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                Author and article information

                Contributors
                +31-20-4440953 , +31-20-4443688 , gams.vandongen@vumc.nl
                Journal
                Eur J Nucl Med Mol Imaging
                European Journal of Nuclear Medicine and Molecular Imaging
                Springer-Verlag (Berlin/Heidelberg )
                1619-7070
                1619-7089
                18 September 2009
                18 September 2009
                February 2010
                : 37
                : 2
                : 250-259
                Affiliations
                [1 ]Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands
                [2 ]Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
                [3 ]Macrocyclics Inc., Dallas, TX USA
                Article
                1263
                10.1007/s00259-009-1263-1
                2816257
                19763566
                6c7bc0ae-c142-42d4-afa8-c85973818c31
                © The Author(s) 2009
                History
                : 16 June 2009
                : 14 August 2009
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2010

                Radiology & Imaging
                desferrioxamine,radiolabeling,positron emission tomography,bifunctional chelate,zirconium-89,antibodies

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