Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates
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 68 Ga would permit the use of positron emission tomography (PET), providing better resolution, sensitivity,...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2014-12-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2014.00034 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841563193141362688 |
|---|---|
| author | Hadis Honarvar Joanna Strand Anna Perols Anna Orlova Ram Kumar Selvaraju Amelie Eriksson Karlström Vladimir Tolmachev |
| author_facet | Hadis Honarvar Joanna Strand Anna Perols Anna Orlova Ram Kumar Selvaraju Amelie Eriksson Karlström Vladimir Tolmachev |
| author_sort | Hadis Honarvar |
| collection | DOAJ |
| description | 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 68 Ga 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 Z HER2: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 68 Ga- and 111 In-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 68 Ga-labeled Affibody molecules than for the 111 In-labeled counterparts. The best 68 Ga-labeled variant was 68 Ga-[DOTA-A1]-Z HER2: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. 111 In-[DOTA-A 1 ]-Z HER2:S1 and 111 In-[DOTA-K 58 ]-Z HER2: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. |
| format | Article |
| id | doaj-art-0f1eff2373814c25aeda244426c445c4 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2014-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-0f1eff2373814c25aeda244426c445c42025-01-03T00:10:25ZengSAGE PublishingMolecular Imaging1536-01212014-12-011310.2310/7290.2014.0003410.2310_7290.2014.00034Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled ConjugatesHadis HonarvarJoanna StrandAnna PerolsAnna OrlovaRam Kumar SelvarajuAmelie Eriksson KarlströmVladimir TolmachevAffibody 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 68 Ga 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 Z HER2: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 68 Ga- and 111 In-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 68 Ga-labeled Affibody molecules than for the 111 In-labeled counterparts. The best 68 Ga-labeled variant was 68 Ga-[DOTA-A1]-Z HER2: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. 111 In-[DOTA-A 1 ]-Z HER2:S1 and 111 In-[DOTA-K 58 ]-Z HER2: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.https://doi.org/10.2310/7290.2014.00034 |
| spellingShingle | Hadis Honarvar Joanna Strand Anna Perols Anna Orlova Ram Kumar Selvaraju Amelie Eriksson Karlström Vladimir Tolmachev Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates 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 Ga-Compared to In-Labeled Conjugates |
| title_full | Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates |
| title_fullStr | Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates |
| title_full_unstemmed | Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates |
| title_short | Position for Site-Specific Attachment of a DOTA Chelator to Synthetic Affibody Molecules Has a Different Influence on the Targeting Properties of Ga-Compared to In-Labeled Conjugates |
| title_sort | position for site specific attachment of a dota chelator to synthetic affibody molecules has a different influence on the targeting properties of ga compared to in labeled conjugates |
| url | https://doi.org/10.2310/7290.2014.00034 |
| work_keys_str_mv | AT hadishonarvar positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT joannastrand positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT annaperols positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT annaorlova positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT ramkumarselvaraju positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT amelieerikssonkarlstrom positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates AT vladimirtolmachev positionforsitespecificattachmentofadotachelatortosyntheticaffibodymoleculeshasadifferentinfluenceonthetargetingpropertiesofgacomparedtoinlabeledconjugates |