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A comparative evaluation of the chelators H(4)octapa and CHX-A"-DTPA with the therapeutic radiometal Y-90

TitleA comparative evaluation of the chelators H(4)octapa and CHX-A"-DTPA with the therapeutic radiometal Y-90
Publication TypeJournal Article
Year of Publication2016
AuthorsPrice, EW, Edwards, KJ, Carnazza, KE, Carlin, SD, Zeglis, BM, Adam, MJ, Orvig, C, Lewis, JS
JournalNucl. Med. Biol.
Volume43
Pagination566-576
Date PublishedSEP
ISSN0969-8051
Abstract

Objectives: To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A `'-DTPA and H(4)octapa with the therapeutic radiometal Y-90. Methods: The bifunctional chelators p-SCN-Bn-H(4)octapa and p-SCN-Bn-CHX-A `'-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with Y-90 to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer. Results: High radiochemical yields (>95%) were obtained with Y-90-CHX-A `'-DTPA-trastuzumab and Y-90-octapatrastuzumab after 15 min at room temperature. Both 9 Y-CHX-A `'-DTPA-trastuzumab and Y-90-octapatrastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (423 +/- 4.0 %ID/g for Y-90-CHX-A `'-DTPA-trastuzumab and 30.1 +/- 7.4 %ID/g for Y-90-octapa-trastuzumab at 72 h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, Y-90 radioimmunotherapy studies performed in tumor-bearing mice demonstrated that Y-90-CHX-A `'-DTPA-trastuzumab and Y-90-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls. Conclusions: Ultimately, this work demonstrates that the acyclic chelators CHX-A `'-DTPA and H(4)octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring Y-90. (C) 2016 Elsevier Inc. All rights reserved.

DOI10.1016/j.nucmedbio.2016.06.004