Position for site-specific attachment of a DOTA chelator to synthetic affibody molecules has a different influence on the targeting properties of 68Ga- compared to 111in-labeled conjugates
(2014) In Molecular Imaging 13.- Abstract
Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the C-terminus. The biodistribution of 68Ga- and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers,... (More)
Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the C-terminus. The biodistribution of 68Ga- and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers, and the influence was more pronounced for 68Ga-labeled Affibody molecules than for the 111In-labeled counterparts. The best 68Ga-labeled variant was 68Ga-[DOTA-A1]-ZHER2:S1, which provided a tumor uptake of 13 ± 1 %ID/g and a tumor to blood ratio of 39 ± 12 at 2 hours after injection. 111In-[DOTA-A1]-ZHER2:S1 and 111In-[DOTA-K58]-ZHER2:S1 were equally good at this time point, providing a tumor uptake of 15 to 16 %ID/g and a tumor to blood ratio in the range of 60 to 80. In conclusion, the selection of the best position for a chelator in Affibody molecules can be used for optimization of their imaging properties. This may be important for the development of Affibody-based and other protein-based imaging probes.
(Less)
- author
- Honarvar, Hadis ; Strand, Joanna LU ; Perols, Anna ; Orlova, Anna ; Selvaraju, Ram Kumar ; Eriksson Karlström, Amelie and Tolmachev, Vladimir
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Cell Line, Tumor, Chelating Agents/chemistry, Female, Gallium Radioisotopes/pharmacokinetics, Heterocyclic Compounds, 1-Ring/chemistry, Humans, Indium Radioisotopes/pharmacokinetics, Isotope Labeling, Mice, Neoplasm Transplantation, Ovarian Neoplasms/diagnostic imaging, Positron-Emission Tomography, Recombinant Fusion Proteins/chemical synthesis
- in
- Molecular Imaging
- volume
- 13
- publisher
- BC Decker
- external identifiers
-
- scopus:84918563830
- pmid:25249017
- ISSN
- 1535-3508
- DOI
- 10.2310/7290.2014.00034
- language
- English
- LU publication?
- no
- id
- c821c59b-5004-4688-ac29-0b7018a50172
- date added to LUP
- 2022-11-16 13:39:28
- date last changed
- 2024-01-03 11:15:50
@article{c821c59b-5004-4688-ac29-0b7018a50172, abstract = {{<p>Affibody molecules, small (7 kDa) scaffold proteins, are a promising class of probes for radionuclide molecular imaging. Radiolabeling of Affibody molecules with the positron-emitting nuclide 68Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity, and quantification accuracy than single-photon emission computed tomography (SPECT). The synthetic anti-HER2 ZHER2:S1 Affibody molecule was conjugated with DOTA at the N-terminus, in the middle of helix 3, or at the C-terminus. The biodistribution of 68Ga- and 111In-labeled Affibody molecules was directly compared in NMRI nu/nu mice bearing SKOV3 xenografts. The position of the chelator strongly influenced the biodistribution of the tracers, and the influence was more pronounced for 68Ga-labeled Affibody molecules than for the 111In-labeled counterparts. The best 68Ga-labeled variant was 68Ga-[DOTA-A1]-ZHER2:S1, which provided a tumor uptake of 13 ± 1 %ID/g and a tumor to blood ratio of 39 ± 12 at 2 hours after injection. 111In-[DOTA-A1]-ZHER2:S1 and 111In-[DOTA-K58]-ZHER2:S1 were equally good at this time point, providing a tumor uptake of 15 to 16 %ID/g and a tumor to blood ratio in the range of 60 to 80. In conclusion, the selection of the best position for a chelator in Affibody molecules can be used for optimization of their imaging properties. This may be important for the development of Affibody-based and other protein-based imaging probes.</p>}}, author = {{Honarvar, Hadis and Strand, Joanna and Perols, Anna and Orlova, Anna and Selvaraju, Ram Kumar and Eriksson Karlström, Amelie and Tolmachev, Vladimir}}, issn = {{1535-3508}}, keywords = {{Animals; Cell Line, Tumor; Chelating Agents/chemistry; Female; Gallium Radioisotopes/pharmacokinetics; Heterocyclic Compounds, 1-Ring/chemistry; Humans; Indium Radioisotopes/pharmacokinetics; Isotope Labeling; Mice; Neoplasm Transplantation; Ovarian Neoplasms/diagnostic imaging; Positron-Emission Tomography; Recombinant Fusion Proteins/chemical synthesis}}, language = {{eng}}, publisher = {{BC Decker}}, series = {{Molecular Imaging}}, title = {{Position for site-specific attachment of a DOTA chelator to synthetic affibody molecules has a different influence on the targeting properties of 68Ga- compared to 111in-labeled conjugates}}, url = {{http://dx.doi.org/10.2310/7290.2014.00034}}, doi = {{10.2310/7290.2014.00034}}, volume = {{13}}, year = {{2014}}, }