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Synthesis and chara...
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Blom, ElisabethUppsala universitet,Institutionen för biokemi och organisk kemi,Bengt Långström
(author)
Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-08-08
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Wiley,2011
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-108589
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-108589URI
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https://doi.org/10.1002/jlcr.1909DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Vascular endothelial growth factor (VEGF) signaling via vascular endothelial growth factor receptor 2 (VEGFR-2) on tumor endothelial cells is a critical driver of tumor angiogenesis. Novel anti-angiogenic drugs target VEGF/VEGFR-2 signaling and induce changes in VEGFR-2 prevalence. To monitor VEGFR-2 prevalence in the course of treatment, we are evaluating (68)Ga positron emission tomography imaging agents based on macrocyclic chelators, site-specifically conjugated via polyethylene glycol (PEG) linkers to engineered VEGFR-2 ligand, single-chain (sc) VEGF. The (68)Ga-labeling was performed at room temperature with NOTA (2,2', 2 ''-(1,4,7-triazonane-1,4,7-triyl) triacetic acid) conjugates or at 90 degrees C by using either conventional or microwave heating with NOTA and DOTA (2,2', 2 '', 2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid) conjugates. The fastest (similar to 2min) and the highest incorporation (>90%) of (68)Ga into conjugate that resulted in the highest specific radioactivity (similar to 400MBq/nmol) was obtained with microwave heating of the conjugates. The bioactivity of the NOTA-and DOTA-containing tracers was validated in 3-D tissue culture model of 293/KDR cells engineered to express high levels of VEGFR-2. The NOTA-containing tracer also displayed a rapid accumulation (similar to 20s after intravenous injection) to steady-state level in xenograft tumor models. A combination of high specific radioactivity and maintenance of functional activity suggests that scVEGF-PEG-[(68)Ga] NOTA and scVEGF-PEG-[(68)Ga] DOTA might be promising tracers for monitoring VEGFR-2 prevalence and should be further explored.
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Velikyan, IrinaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)irinveli
(author)
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Monazzam, AzitaUppsala universitet,Endokrin tumörbiologi(Swepub:uu)azmon677
(author)
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Razifar, PashaUppsala universitet,Centrum för bildanalys,Bildanalys och människa-datorinteraktion(Swepub:uu)serra226
(author)
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Nair, Manoj
(author)
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Razifar, Payam
(author)
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Vanderheyden, Jean-Luc
(author)
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Krivoshein, Arcadius V.
(author)
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Backer, Marina
(author)
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Backer, Joseph
(author)
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Långström, BengtUppsala universitet,Institutionen för biokemi och organisk kemi(Swepub:uu)benglang
(author)
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Uppsala universitetInstitutionen för biokemi och organisk kemi
(creator_code:org_t)
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In:Journal of labelled compounds & radiopharmaceuticals: Wiley54:11, s. 685-6920362-48031099-1344
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Blom, Elisabeth
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Velikyan, Irina
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Monazzam, Azita
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Razifar, Pasha
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Nair, Manoj
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Razifar, Payam
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Vanderheyden, Je ...
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Krivoshein, Arca ...
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Backer, Marina
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Backer, Joseph
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Långström, Bengt
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Uppsala University