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Synthesis and characterization of scVEGF-PEG-[68Ga]NOTA and scVEGF-PEG-[68Ga]DOTA PET tracers

Blom, Elisabeth (author)
Uppsala universitet,Institutionen för biokemi och organisk kemi,Bengt Långström
Velikyan, Irina (author)
Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
Monazzam, Azita (author)
Uppsala universitet,Endokrin tumörbiologi
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Razifar, Pasha (author)
Uppsala universitet,Centrum för bildanalys,Bildanalys och människa-datorinteraktion
Nair, Manoj (author)
Razifar, Payam (author)
Vanderheyden, Jean-Luc (author)
Krivoshein, Arcadius V. (author)
Backer, Marina (author)
Backer, Joseph (author)
Långström, Bengt (author)
Uppsala universitet,Institutionen för biokemi och organisk kemi
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 (creator_code:org_t)
2011-08-08
2011
English.
In: Journal of labelled compounds & radiopharmaceuticals. - : Wiley. - 0362-4803 .- 1099-1344. ; 54:11, s. 685-692
Related links:
https://urn.kb.se/re...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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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.

Subject headings

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)
NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)
TEKNIK OCH TEKNOLOGIER  -- Medicinteknik -- Medicinsk bildbehandling (hsv//swe)
ENGINEERING AND TECHNOLOGY  -- Medical Engineering -- Medical Image Processing (hsv//eng)

Keyword

scVEGF
(68)Ga
radiolabeling
angiogenesis
VEGFR-2
PET

Publication and Content Type

ref (subject category)
art (subject category)

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