Three Methods for 18F Labeling of the HER2-Binding Affibody Molecule ZHER2:2891 Including Preclinical Assessment
| Autor: | Matthias Glaser, Bard Indrevoll, Joseph Arukwe, Antonios Danikas, Anthony Wilson, Duncan Hiscock, Susan Hoppmann, Rajiv Bhalla, Peter Iveson |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Journal of Nuclear Medicine. 54:1981-1988 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | Human epidermal growth factor receptor (HER2)–targeted Affibody molecules radiolabeled with 18F allow the noninvasive assessment of HER2 status in vivo through PET imaging. Such agents have the potential to improve patient management by selecting individuals for HER2-targeted therapies and allowing therapy monitoring. The aim of this study was to assess different 18F radiolabeling strategies of the HER2-specific Affibody molecule ZHER2:2891, preclinically determine the biologic efficacy of the different radiolabel molecules, and select a preferred radiolabeling strategy to progress for automated manufacture. Methods: Cysteine was added to the C terminus of the Affibody molecule for the coupling of maleimide linkers, and 3 radiolabeling strategies were assessed: silicon-fluoride acceptor approach (18F-SiFA), 18F-AlF-NOTA, and 4-18F-fluorobenzaldehyde (18F-FBA). The biodistributions of the radiolabeled Affibody molecules were then determined in naive CD-1 nude mice, and tumor targeting was assessed in CD-1 nude mice bearing high-HER2-expressing NCI-N87 tumors and low-HER2-expressing A431 tumors. The 111In-ABY-025 compound, which has demonstrable clinical utility, served as a reference tracer. Results: The non–decay-corrected radiochemical yields based on starting 18F-fluoride using the 18F-FBA, 18F-SiFA, and 18F-AlF-NOTA methods were 13% ± 3% (n = 5), 38% ± 2% (n = 3), and 11% ± 4% (n = 6), respectively. In naive mice, both the 18F-AlF-NOTA-ZHER2:2891 and the 111In-ABY-025 compounds showed a significant kidney retention (70.3 ± 1.3 and 73.8 ± 3.0 percentage injected dose [%ID], respectively, at 90 min after injection), which was not observed for 18F-FBA-ZHER2:2891 or 18F-SiFA-ZHER2:2891 (4.8 ± 0.6 and 10.1 ± 0.7 %ID, respectively, at 90 min). The 18F-SiFA-ZHER2:2891 conjugate was compromised by increasing bone retention over time (5.3 ± 1.0 %ID/g at 90 min after injection), indicating defluorination. All the radiolabeled Affibody molecules assessed showed significantly higher retention in NCI-N87 tumors than A431 tumors at all time points (P |
| Databáze: | OpenAIRE |
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