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

Fook T Lee; Ingrid J G Burvenich; Nancy Guo; Pece Kocovski; Henri Tochon-Danguy; Uwe Ackermann; Graeme J O'Keefe; Sylvia Gong; Angela Rigopoulos; Zhanqi Liu; Hui K Gan; Andrew M Scott

doi:10.1177/1536012116647535

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

Mol Imaging. 2016 Jul 25:15:1536012116647535. doi: 10.1177/1536012116647535. Print 2016.

Authors

Affiliations

¹ Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia ft.lee@onjcri.org.au.
² Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
³ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
⁴ 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.

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.

Keywords: antibodies; immuno-PET; internalization; iodine-124; residualizing peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / pharmacokinetics*
Brain Neoplasms / diagnostic imaging*
Cell Line, Tumor
Glioblastoma / diagnostic imaging*
Humans
Iodine Radioisotopes / chemistry
Mice
Neoplasm Transplantation
Peptides / chemistry
Peptides / pharmacokinetics*
Radiopharmaceuticals / chemistry
Tissue Distribution
Tyrosine

Substances

Antibodies, Monoclonal
Iodine Radioisotopes
Peptides
Radiopharmaceuticals
Tyrosine