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Cyclic versus Noncy...
Cyclic versus Noncyclic Chelating Scaffold for 89Zr-Labeled ZEGFR:2377 Affibody Bioconjugates Targeting Epidermal Growth Factor Receptor Overexpression
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- Summer, D. (författare)
- Med Univ Innsbruck, Dept Nucl Med, Anichstr 35, A-6020 Innsbruck, Austria.
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- Garousi, Javad (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Oroujeni, Maryam (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Mitran, Bogdan (författare)
- Uppsala universitet,Avdelningen för Molekylär Avbildning
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- Andersson, Ken G. (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden.
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- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Löfblom, John (författare)
- KTH,Proteinteknologi,KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, Sweden.
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Avdelningen för Molekylär Avbildning
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Decristoforo, C. (författare)
- Med Univ Innsbruck, Dept Nucl Med, Anichstr 35, A-6020 Innsbruck, Austria.
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Med Univ Innsbruck, Dept Nucl Med, Anichstr 35, A-6020 Innsbruck, Austria Medicinsk strålningsvetenskap (creator_code:org_t)
- 2017-12-01
- 2018
- Engelska.
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 15:1, s. 175-185
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Abstract
Ämnesord
Stäng
- Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure. This study was designed to compare FSC and DFO head-to-head as bifunctional chelators for 89Zr-radiolabeled EGFR-targeting ZEGFR:2377 affibody bioconjugates. FSC-ZEGFR:2377 and DFO-ZEGFR:2377 were evaluated regarding radiolabeling, in vitro stability, specificity, cell uptake, receptor affinity, biodistribution, and microPET-CT imaging. Both conjugates were efficiently labeled with zirconium-89 at room temperature but radiochemical yields increased substantially at elevated temperature, 85 °C. Both 89Zr-FSC-ZEGFR:2377 and 89Zr-DFO-ZEGFR:2377 revealed remarkable specificity, affinity and slow cell-line dependent internalization. Radiolabeling at 85 °C showed comparable results in A431 tumor xenografted mice with minor differences regarding blood clearance, tumor and liver uptake. In comparison 89Zr-DFO-ZEGFR:2377, radiolabeled at room temperature, showed a significant difference regarding tumor-to-organ ratios. MicroPET-CT imaging studies of 89Zr-FSC-ZEGFR:2377 as well as 89Zr-DFO-ZEGFR:2377 confirmed these findings. In summary we were able to show that FSC is a suitable alternative to DFO for radiolabeling of biomolecules with zirconium-89. Furthermore, our findings indicate that 89Zr-radiolabeling of DFO conjugates at higher temperature reduces off-chelate binding leading to significantly improved tumor-to-organ ratios and therefore enhancing image contrast.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- affibody
- DFO
- EGFR
- FSC
- PET
- zirconium-89
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Summer, D.
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Garousi, Javad
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Oroujeni, Maryam
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Mitran, Bogdan
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Andersson, Ken G ...
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Vorobyeva, Anzhe ...
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visa fler...
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Löfblom, John
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Orlova, Anna, 19 ...
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Tolmachev, Vladi ...
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Decristoforo, C.
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Uppsala universitet