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

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 radiolabel...

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Bibliographic Details
Published in:	Molecular imaging Vol. 15
Main Authors:	Fook T. Lee PhD, Ingrid J. G. Burvenich PhD, Nancy Guo MBBS, MSc, Pece Kocovski BSc (Honors), Henri Tochon-Danguy PhD, Uwe Ackermann PhD, Graeme J. O’Keefe PhD, Sylvia Gong PhD, Angela Rigopoulos BSc, MSc, Zhanqi Liu MBBS, PhD, Hui K. Gan MBBS, FRACP, PhD, Andrew M. Scott MBBS, FRACP, MD
Format:	Journal Article
Language:	English
Published:	SAGE Publications 01-06-2016
Online Access:	Get full text
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Summary:	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-PEG 4 -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-PEG 4 -tptddYddtpt-ch806 tumor uptake was similar to 111 In-CHX-A″-DTPA-ch806. 125 I-PEG 4 -tptddyddtpt-ch806 showed a lower tumor uptake value but higher than directly labeled 125 I-ch806. 124 I-PEG 4 -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-PEG 4 -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, d Thr- d Pro- d Thr- dA sp -dA sp-Tyr -dA sp -dA sp- d Thr- d Pro- d Thr, 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.
ISSN:	1536-0121
DOI:	10.1177/1536012116647535