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Title: L-Tyrosine confers residualizing properties to a d-Amino acid-rich residualizing peptide for radioiodination of internalizing antibodies
Austin Authors: Lee, Fook T;Burvenich, Ingrid JG;Guo, Nancy;Kocovski, Pece;Tochon-Danguy, Henri;Ackermann, Uwe ;O’Keefe, Graeme J;Gong, Sylvia;Rigopoulos, Angela;Liu, Zhanqi;Gan, Hui K ;Scott, Andrew M 
Affiliation: Austin Health, Heidelberg, Victoria, Australia
Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 2016
Date: 2016-07-25
Publication information: Molecular Imaging 2016; online first: 25 July
Abstract: PURPOSE: The aims of the study were to develop and evaluate a novel residualizing peptide for labeling internalizing antibodies with (124)I 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 (124)I-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 (131)I-PEG4-tptddYddtpt-ch806 tumor uptake was similar to (111)In-CHX-A″-DTPA-ch806. (125)I-PEG4-tptddyddtpt-ch806 showed a lower tumor uptake value but higher than directly labeled (125)I-ch806. (124)I-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 (124)I-PEG4-tptddYddtpt-ch806 was similar to (111)In-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 (124)I for high-resolution immuno-PET imaging of tumors and for evaluation in early-phase clinical trials.
DOI: 10.1177/1536012116647535
Journal: Molecular Imaging
PubMed URL:
Type: Journal Article
Subjects: Residualizing peptide
Appears in Collections:Journal articles

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