-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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2016-06-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012116647535 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841563183660138496 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Fook T. Lee PhD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ec906d2158ff44d483cd65511d1e09d3 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2016-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-ec906d2158ff44d483cd65511d1e09d32025-01-03T00:10:43ZengSAGE PublishingMolecular Imaging1536-01212016-06-011510.1177/153601211664753510.1177_1536012116647535-Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing AntibodiesFook T. Lee PhD0Ingrid J. G. Burvenich PhD1Nancy Guo MBBS, MSc2Pece Kocovski BSc (Honors)3Henri Tochon-Danguy PhD4Uwe Ackermann PhD5Graeme J. O’Keefe PhD6Sylvia Gong PhD7Angela Rigopoulos BSc, MSc8Zhanqi Liu MBBS, PhD9Hui K. Gan MBBS, FRACP, PhD10Andrew M. Scott MBBS, FRACP, MD11 Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, 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 Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, 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, AustraliaPurpose: 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.https://doi.org/10.1177/1536012116647535 |
| spellingShingle | 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 -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies Molecular Imaging |
| title | -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies |
| title_full | -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies |
| title_fullStr | -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies |
| title_full_unstemmed | -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies |
| title_short | -Tyrosine Confers Residualizing Properties to a -Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies |
| title_sort | tyrosine confers residualizing properties to a amino acid rich residualizing peptide for radioiodination of internalizing antibodies |
| url | https://doi.org/10.1177/1536012116647535 |
| work_keys_str_mv | AT fooktleephd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT ingridjgburvenichphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT nancyguombbsmsc tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT pecekocovskibschonors tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT henritochondanguyphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT uweackermannphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT graemejokeefephd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT sylviagongphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT angelarigopoulosbscmsc tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT zhanqiliumbbsphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT huikganmbbsfracpphd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies AT andrewmscottmbbsfracpmd tyrosineconfersresidualizingpropertiestoaaminoacidrichresidualizingpeptideforradioiodinationofinternalizingantibodies |