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Influence of Nuclid...
Influence of Nuclides and Chelators on Imaging Using Affibody Molecules : Comparative Evaluation of Recombinant Affibody Molecules Site-Specifically Labeled with Ga-68 and In-111 via Maleimido Derivatives of DOTA and NODAGA
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- Altai, Mohamed (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Strand, Joanna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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Rosik, Daniel (författare)
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- Selvaraju, Ram Kumar (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Eriksson Karlström, Amelie (författare)
- KTH,Molekylär Bioteknologi,Albanova VinnExcellence Center for Protein Technology, ProNova
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- Orlova, Anna (författare)
- Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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(creator_code:org_t)
- 2013-06-05
- 2013
- Engelska.
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 24:6, s. 1102-1109
- Relaterad länk:
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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
- Accurate detection of cancer-associated molecular abnormalities in tumors could make cancer treatment more of personalized. Affibody molecules enable high contrast imaging of tumor-associated protein expression shortly after injection. The use should increase sensitivity of HER2 imaging. The chemical nature of the generator-produced positron-emitting radionuclide Ga-68 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 Z(HER2:2395) HER2-binding Affibody molecule with Ga-68. DOTA and NODAGA were site-specifically conjugated to the Z(HER2:2395) Affibody molecule having a C-terminal cysteine and labeled with Ga-68 and In-111. 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 dearly visualized using all conjugates. The influence of chelator on the biodistribution and targeting properties was much less pronounced for Ga-68 than for In-111. The tumor uptake of Ga-68-NODAGA-Z(HER2:2395) and Ga-68-NODAGA-Z(HER2:2395) and tumor-to-blood ratios at 2 h p.i. did not differ significantly. However, the tumor-to-liver ratio was significantly higher for Ga-68-NODAGA- Z(HER2:2395) (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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Nyckelord
- affibody molecule
- chelating agent
- epidermal growth factor receptor 2
- gallium 68
- indium 111
- maleimido derivative
- recombinant protein
- unclassified drug
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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