L-Tyrosine Confers Residualizing Properties to a D-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies
AuthorLee, FT; Burvenich, IJG; Guo, N; Kocovski, P; Tochon-Danguy, H; Ackermann, U; O'Keefe, GJ; Gong, S; Rigopoulos, A; Liu, Z; ...
Source TitleMolecular Imaging
PublisherSAGE PUBLICATIONS INC
University of Melbourne Author/sBURVENICH, INGRID; Scott, Andrew; Liu, Zhanqi; TOCHON-DANGUY, HENRI; Gan, Hui; LEE, FOOK-THEAN; Gong, Sylvia; O'Keefe, Graeme
AffiliationMedicine and Radiology
School of Physics
Document TypeJournal Article
CitationsLee, F. T., Burvenich, I. J. G., Guo, N., Kocovski, P., Tochon-Danguy, H., Ackermann, U., O'Keefe, G. J., Gong, S., Rigopoulos, A., Liu, Z., Gan, H. K. & Scott, A. M. (2016). L-Tyrosine Confers Residualizing Properties to a D-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies. MOLECULAR IMAGING, 15, pp.1-9. https://doi.org/10.1177/1536012116647535.
Access StatusOpen Access
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.
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