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Residualising peptide 2016 FT Lee.pdf (480.09 kB)

L-Tyrosine Confers Residualizing Properties to a D-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies

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posted on 2021-08-13, 01:56 authored by Fook-Thean LeeFook-Thean Lee, IJG Burvenich, N Guo, Pece Kocovski, H Tochon-Danguy, Uwe AckermannUwe Ackermann, GJ O'Keefe, Sylvia GongSylvia Gong, Angela RigopoulosAngela Rigopoulos, Z Liu, Hui GanHui Gan, Andrew ScottAndrew Scott
Purpose: The aims of the study were to develop and evaluate a novel residualizing peptide for labeling internalizing antibodies with 124I to support clinical development using immuno-positron emission tomography (PET). Methods: The anti-epidermal growth factor receptor antibody ch806 was radiolabeled directly or indirectly with isotopes and various residualizing peptides. Azido-derivatized radiolabeled peptides were conjugated to dibenzylcyclooctyne-derivatized ch806 antibody via click chemistry. The radiochemical purities, antigen-expressing U87MG.de2-7 human glioblastoma cell-binding properties, and targeting of xenografts at 72 hours post injection of all radioconjugates were compared. Biodistribution of 124I-PEG4-tptddYddtpt-ch806 and immuno-PET imaging were evaluated in tumor-bearing mice. Results: Biodistribution studies using xenografts at 72 hours post injection showed that 131I-PEG4-tptddYddtpt-ch806 tumor uptake was similar to 111In-CHX-A″-DTPA-ch806. 125I-PEG4-tptddyddtpt-ch806 showed a lower tumor uptake value but higher than directly labeled 125I-ch806. 124I-PEG4-tptddYddtpt-ch806 was produced at 23% labeling efficiency, 98% radiochemical purity, 25.9 MBq/mg specific activity, and 64% cell binding in the presence of antigen excess. Tumor uptake for 124I-PEG4-tptddYddtpt-ch806 was similar to 111In-CHX-A″-DTPA-ch806. High-resolution immuno-PET/magnetic resonance imaging of tumors showed good correlation with biodistribution data. Conclusions: The mixed d/l-enantiomeric peptide, dThr-dPro-dThr-dAsp-dAsp-Tyr-dAsp-dAsp-dThr-dPro-dThr, is suitable for radiolabeling antibodies with radiohalogens such as 124I for high-resolution immuno-PET imaging of tumors and for evaluation in early-phase clinical trials.


The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported in part by NHMRC Project grant 1003085 and NHMRC Program grant 487922. Operational Infrastructure Support Program funding was provided by the Victorian Government and funds to purchase the imaging equipment was provided by the Australian Cancer Research Foundation.


Publication Date



Molecular Imaging




9p. (p. 1-9)





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