A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal 90Y Journal Article
| Authors: | Price, E. W.; Edwards, K. J.; Carnazza, K. E.; Carlin, S. D.; Zeglis, B. M.; Adam, M. J.; Orvig, C.; Lewis, J. S. |
| Article Title: | A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal 90Y |
| Abstract: | Objectives To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal 90Y. Methods The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with 90Y 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 90Y-CHX-A″-DTPA-trastuzumab and 90Y-octapa-trastuzumab after 15 min at room temperature. Both 90Y-CHX-A″-DTPA-trastuzumab and 90Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3 ± 4.0 %ID/g for 90Y-CHX-A″-DTPA-trastuzumab and 30.1 ± 7.4 %ID/g for 90Y-octapa-trastuzumab at 72 h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, 90Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that 90Y-CHX-A″-DTPA-trastuzumab and 90Y-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 H4octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring 90Y. © 2016 Elsevier Inc. |
| Keywords: | trastuzumab; radioimmunotherapy; yttrium-90; radiometal; chx-a″-dtpa; h4octapa |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 43 |
| Issue: | 9 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2016-09-01 |
| Start Page: | 566 |
| End Page: | 576 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2016.06.004 |
| PROVIDER: | scopus |
| PUBMED: | 27419360 |
| PMCID: | PMC4992617 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2016 -- Source: Scopus |
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