title: L-Tyrosine Confers Residualizing Properties to a d-Amino Acid-Rich Residualizing Peptide for Radioiodination of Internalizing Antibodies.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia ft.lee@onjcri.org.au.
authors.forename: Fook T
authors.initials: FT
authors.lastname: Lee
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Ingrid J G
authors.initials: IJ
authors.lastname: Burvenich
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Nancy
authors.initials: N
authors.lastname: Guo
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Pece
authors.initials: P
authors.lastname: Kocovski
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Henri
authors.initials: H
authors.lastname: Tochon-Danguy
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Uwe
authors.initials: U
authors.lastname: Ackermann
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: O'Keefe
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Gong
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Rigopoulos
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Zhanqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tumour Targeting Program, Ludwig Institute For Cancer Research and Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
authors.forename: Hui K
authors.initials: HK
authors.lastname: Gan
authors.affiliation: 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.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D051379:Mice; D009368:Neoplasm Transplantation; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000737:chemistry; D014018:Tissue Distribution; D014443:Tyrosine
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals; D014443:Tyrosine
keywords: antibodies; immuno-PET; internalization; iodine-124; residualizing peptide