Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re
(2014) In European Journal of Medicinal Chemistry 87. p.28-519- Abstract
Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after... (More)
Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
(Less)
- author
- publishing date
- 2014-11-24
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amino Acid Sequence, Animals, Cell Line, Tumor, Chelating Agents/chemistry, Cysteine/analysis, Humans, Mice, Molecular Sequence Data, Peptides/chemistry, Radioisotopes/chemistry, Recombinant Fusion Proteins/chemistry, Rhenium/chemistry, Sequence Homology, Amino Acid
- in
- European Journal of Medicinal Chemistry
- volume
- 87
- pages
- 28 - 519
- publisher
- Elsevier Masson SAS
- external identifiers
-
- scopus:84907818093
- pmid:25282673
- ISSN
- 0223-5234
- DOI
- 10.1016/j.ejmech.2014.09.082
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2014 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
- id
- 65fed389-4c8e-4694-93f5-a8b7e2af6da5
- date added to LUP
- 2022-11-16 13:38:57
- date last changed
- 2024-04-04 06:18:43
@article{65fed389-4c8e-4694-93f5-a8b7e2af6da5,
abstract = {{<p>Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.</p>}},
author = {{Altai, Mohamed and Honarvar, Hadis and Wållberg, Helena and Strand, Joanna and Varasteh, Zohreh and Rosestedt, Maria and Orlova, Anna and Dunås, Finn and Sandström, Mattias and Löfblom, John and Tolmachev, Vladimir and Ståhl, Stefan}},
issn = {{0223-5234}},
keywords = {{Amino Acid Sequence; Animals; Cell Line, Tumor; Chelating Agents/chemistry; Cysteine/analysis; Humans; Mice; Molecular Sequence Data; Peptides/chemistry; Radioisotopes/chemistry; Recombinant Fusion Proteins/chemistry; Rhenium/chemistry; Sequence Homology, Amino Acid}},
language = {{eng}},
month = {{11}},
pages = {{28--519}},
publisher = {{Elsevier Masson SAS}},
series = {{European Journal of Medicinal Chemistry}},
title = {{Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re}},
url = {{http://dx.doi.org/10.1016/j.ejmech.2014.09.082}},
doi = {{10.1016/j.ejmech.2014.09.082}},
volume = {{87}},
year = {{2014}},
}