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Influence of Macroc...
Influence of Macrocyclic Chelators on the Targeting Properties of Ga-68-Labeled Synthetic Affibody Molecules : Comparison with In-111-Labeled Counterparts
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- Strand, Joanna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Honarvar, Hadis (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Perols, Anna (författare)
- KTH,Proteinteknologi
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- Orlova, Anna (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Selvaraju, Ram Kumar (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Eriksson Karlström, Amelie (författare)
- KTH,Proteinteknologi
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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(creator_code:org_t)
- 2013-08-01
- 2013
- Engelska.
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e70028-
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Affibody molecules are a class of small (7 kDa) non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET) would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide Ga-68 (T-1/2 = 67.6 min). Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) and 1-(1,3-carboxypropyl)-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA) were conjugated to the N-terminus of the synthetic Affibody molecule Z(HER2:S1) targeting HER2. Affibody molecules were labeled with Ga-68, and their binding specificity and cellular processing were evaluated. The biodistribution of Ga-68-DOTA-Z(HER2:S1), Ga-68-NOTA-Z(HER2:S1) and Ga-68-NODAGA-Z(HER2:S1), as well as that of their In-111-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for Ga-68-DOTA-Z(HER2:S1) (17.9 +/- 0.7%IA/g) was significantly higher than for both Ga-68-NODAGA-Z(HER2:S1) (16.13 +/- 0.67%IA/g) and Ga-68-NOTA-Z(HER2:S1) (13 +/- 3%IA/g) at 2 h after injection. Ga-68-NODAGA-Z(HER2:S1) had the highest tumor-to-blood ratio (60 +/- 10) in comparison with both Ga-68-DOTA-Z(HER2:S1) (28 +/- 4) and Ga-68-NOTA-Z(HER2:S1) (42 +/- 11). The tumor-to-liver ratio was also higher for Ga-68-NODAGA-Z(HER2:S1) (7 +/- 2) than the DOTA and NOTA conjugates (5.5 +/- 0.6 vs. 3.3 +/- 0.6). The influence of chelator on the biodistribution and targeting properties was less pronounced for Ga-68 than for In-111. The results of this study demonstrate that macrocyclic chelators conjugated to the N-terminus have a substantial influence on the biodistribution of HER2-targeting Affibody molecules labeled with Ga-68. This can be utilized to enhance the imaging contrast of PET imaging using Affibody molecules and improve the sensitivity of molecular imaging. The study demonstrated an appreciable difference of chelator influence for Ga-68 and In-111.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Prostate-Cancer Xenografts
- Breast-Cancer
- In-Vivo
- Somatostatin Analog
- Mouse Model
- In-111
- Dota
- Biodistribution
- Expression
- Affinity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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