Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers
2011 (English)In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 54, no 11, 685-692 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 54, no 11, 685-692 p.
scVEGF, (68)Ga, radiolabeling, angiogenesis, VEGFR-2, PET
Organic Chemistry Medical Image Processing
IdentifiersURN: urn:nbn:se:uu:diva-108589DOI: 10.1002/jlcr.1909ISI: 000297987200001OAI: oai:DiVA.org:uu-108589DiVA: diva2:254747