Influence of nuclides and chelators on imaging using affibody molecules : comparative evaluation of recombinant affibody molecules site-specifically labeled with ⁶⁸Ga and ¹¹¹In via maleimido derivatives of DOTA and NODAGA
(2013) In Bioconjugate Chemistry 24(6). p.9-1102- Abstract
Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant ZHER2:2395 HER2-binding Affibody molecule with (68)Ga. DOTA and NODAGA were site-specifically... (More)
Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant ZHER2:2395 HER2-binding Affibody molecule with (68)Ga. DOTA and NODAGA were site-specifically conjugated to the ZHER2:2395 Affibody molecule having a C-terminal cysteine and labeled with (68)Ga and (111)In. All labeled conjugates retained specificity to HER2 in vitro. Most of the cell-associated activity was membrane-bound with a minor difference in internalization rate. All variants demonstrated specific targeting of xenografts and a high tumor uptake. The xenografts were clearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for (68)Ga than for (111)In. The tumor uptake of (68)Ga-NODAGA-ZHER2:2395 and (68)Ga-DOTA-ZHER2:2395 and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for (68)Ga-NODAGA- ZHER2:2395 (8 ± 2 vs 5.0 ± 0.3) offering the advantage of better liver metastases visualization. In conclusion, influence of chelators on biodistribution of Affibody molecules depends on the radionuclides and reoptimization of labeling chemistry is required when a radionuclide label is changed.
(Less)
- author
- Altai, Mohamed LU ; Strand, Joanna LU ; Rosik, Daniel ; Selvaraju, Ram Kumar ; Eriksson Karlström, Amelie ; Orlova, Anna and Tolmachev, Vladimir
- publishing date
- 2013-06-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acetates/chemistry, Animals, Cell Line, Tumor, Cells, Chelating Agents/chemistry, Female, Gallium Radioisotopes/chemistry, Heterocyclic Compounds, 1-Ring/chemistry, Humans, Indium Radioisotopes/chemistry, Mice, Mice, Inbred BALB C, Mice, Nude, Molecular Structure, Neoplasms, Experimental/diagnosis, Organometallic Compounds/chemistry, Receptor, ErbB-2/analysis, Tissue Distribution
- in
- Bioconjugate Chemistry
- volume
- 24
- issue
- 6
- pages
- 9 - 1102
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:84879389584
- pmid:23705574
- ISSN
- 1520-4812
- DOI
- 10.1021/bc300678y
- language
- English
- LU publication?
- no
- id
- 3c5cf4f2-7aeb-4c8c-bf43-874863fbcc81
- date added to LUP
- 2022-11-16 13:42:27
- date last changed
- 2024-01-03 11:18:15
@article{3c5cf4f2-7aeb-4c8c-bf43-874863fbcc81,
abstract = {{<p>Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use of the generator-produced positron-emitting radionuclide (68)Ga should increase sensitivity of HER2 imaging. The chemical nature of radionuclides and chelators influences the biodistribution of Affibody molecules, providing an opportunity to further increase the imaging contrast. The aim of the study was to compare maleimido derivatives of DOTA and NODAGA for site-specific labeling of a recombinant ZHER2:2395 HER2-binding Affibody molecule with (68)Ga. DOTA and NODAGA were site-specifically conjugated to the ZHER2:2395 Affibody molecule having a C-terminal cysteine and labeled with (68)Ga and (111)In. All labeled conjugates retained specificity to HER2 in vitro. Most of the cell-associated activity was membrane-bound with a minor difference in internalization rate. All variants demonstrated specific targeting of xenografts and a high tumor uptake. The xenografts were clearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for (68)Ga than for (111)In. The tumor uptake of (68)Ga-NODAGA-ZHER2:2395 and (68)Ga-DOTA-ZHER2:2395 and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for (68)Ga-NODAGA- ZHER2:2395 (8 ± 2 vs 5.0 ± 0.3) offering the advantage of better liver metastases visualization. In conclusion, influence of chelators on biodistribution of Affibody molecules depends on the radionuclides and reoptimization of labeling chemistry is required when a radionuclide label is changed.</p>}},
author = {{Altai, Mohamed and Strand, Joanna and Rosik, Daniel and Selvaraju, Ram Kumar and Eriksson Karlström, Amelie and Orlova, Anna and Tolmachev, Vladimir}},
issn = {{1520-4812}},
keywords = {{Acetates/chemistry; Animals; Cell Line, Tumor; Cells; Chelating Agents/chemistry; Female; Gallium Radioisotopes/chemistry; Heterocyclic Compounds, 1-Ring/chemistry; Humans; Indium Radioisotopes/chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplasms, Experimental/diagnosis; Organometallic Compounds/chemistry; Receptor, ErbB-2/analysis; Tissue Distribution}},
language = {{eng}},
month = {{06}},
number = {{6}},
pages = {{9--1102}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Bioconjugate Chemistry}},
title = {{Influence of nuclides and chelators on imaging using affibody molecules : comparative evaluation of recombinant affibody molecules site-specifically labeled with ⁶⁸Ga and ¹¹¹In via maleimido derivatives of DOTA and NODAGA}},
url = {{http://dx.doi.org/10.1021/bc300678y}},
doi = {{10.1021/bc300678y}},
volume = {{24}},
year = {{2013}},
}