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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 ...

  • 2011-08-08
  • Wiley,2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-108589
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-108589URI
  • https://doi.org/10.1002/jlcr.1909DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Velikyan, IrinaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)irinveli (author)
  • Monazzam, AzitaUppsala universitet,Endokrin tumörbiologi(Swepub:uu)azmon677 (author)
  • Razifar, PashaUppsala universitet,Centrum för bildanalys,Bildanalys och människa-datorinteraktion(Swepub:uu)serra226 (author)
  • Nair, Manoj (author)
  • Razifar, Payam (author)
  • Vanderheyden, Jean-Luc (author)
  • Krivoshein, Arcadius V. (author)
  • Backer, Marina (author)
  • Backer, Joseph (author)
  • Långström, BengtUppsala universitet,Institutionen för biokemi och organisk kemi(Swepub:uu)benglang (author)
  • Uppsala universitetInstitutionen för biokemi och organisk kemi (creator_code:org_t)

Related titles

  • In:Journal of labelled compounds & radiopharmaceuticals: Wiley54:11, s. 685-6920362-48031099-1344

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