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Synthesis and characterization of scVEGF‐PEG‐[ 68 Ga]NOTA and scVEGF‐PEG‐[ 68 Ga]DOTA PET tracers
Author(s) -
Blom Elisabeth,
Velikyan Irina,
Monazzam Azita,
Razifar Pasha,
Nair Manoj,
Razifar Payam,
Vanderheyden JeanLuc,
Krivoshein Arcadius V.,
Backer Marina,
Backer Joseph,
Långström Bengt
Publication year - 2011
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1909
Subject(s) - dota , conjugate , chemistry , peg ratio , polyethylene glycol , angiogenesis , ligand (biochemistry) , pegylation , vascular endothelial growth factor , kinase insert domain receptor , radiochemistry , receptor , chelation , cancer research , vegf receptors , biochemistry , vascular endothelial growth factor a , medicine , organic chemistry , mathematical analysis , mathematics , finance , economics
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 °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 (~2 min) and the highest incorporation (>90%) of 68 Ga into conjugate that resulted in the highest specific radioactivity (~400 MBq/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 (~ 20 s 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. Copyright © 2011 John Wiley & Sons, Ltd.