Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMABĀ®
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Date
2020
Authors
Liapis, V.
Tieu, W.
Rudd, S.E.
Donnelly, P.S.
Wittwer, N.L.
Brown, M.P.
Staudacher, A.H.
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EJNMMI Radiopharmacy and Chemistry, 2020; 5(1):27-1-27-15
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Vasilios Liapis, William Tieu, Stacey E. Rudd, Paul S. Donnelly, Nicole L. Wittwer, Michael P. Brown, and Alexander H. Staudacher
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Purpose: The chimeric monoclonal antibody (mAb) chDAB4 (APOMABĀ®) targets the Lupus associated (La)/Sjƶgren 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 ([āøā¹Zr]Zr(IV)) or Iodine-124 ([Ā¹Ā²ā“I]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 [āøā¹Zr]Zr(IV)-labeled chDAB4. Methods: C57BL/6āJ mice bearing subcutaneous syngeneic tumors of EL4 lymphoma were either untreated or given chemotherapy, then administered radiolabeled chDAB4 after 24āh with its biodistribution examined using PET and organ assay. We compared chDAB4 radiolabeled with [āøā¹Zr] Zr(IV) or [Ā¹Ā²ā“I] I, or [āøā¹Zr]Zr-chDAB4 using either DFO-NCS or DFOSq as a chelator. Results: After chemotherapy, [āøā¹Zr]Zr-chDAB4 showed higher and prolonged mean (Ā± SD) tumor uptake of 29.5āĀ±ā5.9 compared to 7.8āĀ±ā1.2 for [Ā¹Ā²ā“I] 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 [āøā¹Zr]Zr-chDAB4 but did alter the tumor:liver ratio in treated mice 3ādays after injection in favour of DFOSq (8.0āĀ±ā1.1) compared to DFO-NCS (4.2āĀ±ā0.7). Conclusion: ImmunoPET using chDAB4 radiolabeled with residualizing [āøā¹Zr] Zr(IV) rather than [Ā¹Ā²ā“I] I optimized post-chemotherapy tumor uptake. Further, PET imaging characteristics were improved by DFOSq rather than DFO-NCS. Therefore, the radionuclide/chelator combination of [āøā¹Zr] Zr(IV) and DFOSq is preferred for the imminent clinical evaluation of chDAB4 as a selective tumor cell death radioligand.
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Ā© 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/.