Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/129688
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Type: Journal article
Title: Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB®
Author: Liapis, V.
Tieu, W.
Rudd, S.E.
Donnelly, P.S.
Wittwer, N.L.
Brown, M.P.
Staudacher, A.H.
Citation: EJNMMI Radiopharmacy and Chemistry, 2020; 5(1):27-1-27-15
Publisher: Springer Nature
Issue Date: 2020
ISSN: 2365-421X
2365-421X
Statement of
Responsibility: 
Vasilios Liapis, William Tieu, Stacey E. Rudd, Paul S. Donnelly, Nicole L. Wittwer, Michael P. Brown, and Alexander H. Staudacher
Abstract: Purpose: The chimeric monoclonal antibody (mAb) chDAB4 (APOMAB®) targets the Lupus associated (La)/Sjögren Syndrome-B (SSB) antigen, which is over-expressed in tumors but only becomes available for antibody binding in dead tumor cells. Hence, chDAB4 may be used as a novel theranostic tool to distinguish between responders and nonresponders early after chemotherapy. Here, we aimed to ascertain which positron emitter, Zirconium-89 ([⁸⁹Zr]Zr(IV)) or Iodine-124 ([¹²⁴I]I), was best suited to label chDAB4 for post-chemotherapy PET imaging of tumor-bearing mice and to determine which of two different bifunctional chelators provided optimal tumor imaging by PET using [⁸⁹Zr]Zr(IV)-labeled chDAB4. Methods: C57BL/6 J mice bearing subcutaneous syngeneic tumors of EL4 lymphoma were either untreated or given chemotherapy, then administered radiolabeled chDAB4 after 24 h with its biodistribution examined using PET and organ assay. We compared chDAB4 radiolabeled with [⁸⁹Zr] Zr(IV) or [¹²⁴I] I, or [⁸⁹Zr]Zr-chDAB4 using either DFO-NCS or DFOSq as a chelator. Results: After chemotherapy, [⁸⁹Zr]Zr-chDAB4 showed higher and prolonged mean (± SD) tumor uptake of 29.5 ± 5.9 compared to 7.8 ± 1.2 for [¹²⁴I] I -chDAB4. In contrast, antibody uptake in healthy tissues was not affected. Compared to DFO-NCS, DFOSq did not result in significant differences in tumor uptake of [⁸⁹Zr]Zr-chDAB4 but did alter the tumor:liver ratio in treated mice 3 days after injection in favour of DFOSq (8.0 ± 1.1) compared to DFO-NCS (4.2 ± 0.7). Conclusion: ImmunoPET using chDAB4 radiolabeled with residualizing [⁸⁹Zr] Zr(IV) rather than [¹²⁴I] I optimized post-chemotherapy tumor uptake. Further, PET imaging characteristics were improved by DFOSq rather than DFO-NCS. Therefore, the radionuclide/chelator combination of [⁸⁹Zr] Zr(IV) and DFOSq is preferred for the imminent clinical evaluation of chDAB4 as a selective tumor cell death radioligand.
Keywords: Zirconium-89; Iodine-124; chDAB4; chemotherapy; PET imaging
Rights: © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 1000031262
DOI: 10.1186/s41181-020-00109-6
Grant ID: http://purl.org/au-research/grants/nhmrc/1126304
Appears in Collections:Molecular and Biomedical Science publications

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