Article

In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft.

Department of Medical Oncology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Journal of Nuclear Medicine (impact factor: 6.38). 09/2007; 48(8):1313-9. DOI:10.2967/jnumed.107.041301 pp.1313-9
Source: PubMed

ABSTRACT Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for noninvasive in vivo VEGF visualization and quantification with the single gamma-emitting isotope 111In and the PET isotope 89Zr.
Labeling, stability, and binding studies were performed. Nude mice with a human SKOV-3 ovarian tumor xenograft were injected with 89Zr-bevacizumab, 111In-bevacizumab, or human 89Zr-IgG. Human 89Zr-IgG served as an aspecific control antibody. Small-animal PET and microCT studies were obtained at 24, 72, and 168 h after injection of 89Zr-bevacizumab and 89Zr-IgG (3.5 +/- 0.5 MBq, 100 +/- 6 microg, 0.2 mL [mean +/- SD]). Small-animal PET and microCT images were fused to calculate tumor uptake and compared with ex vivo biodistribution at 168 h after injection. 89Zr- and 111In-bevacizumab ex vivo biodistribution was compared at 24, 72, and 168 h after injection (2.0 +/- 0.5 MBq each, 100 +/- 4 microg in total, 0.2 mL).
Labeling efficiencies, radiochemical purity, stability, and binding properties were optimal for the radioimmunoconjugates. Small-animal PET showed uptake in well-perfused organs at 24 h and clear tumor localization from 72 h onward. Tumor uptake determined by quantification of small-animal PET images was higher for 89Zr-bevacizumab-namely, 7.38 +/- 2.06 %ID/g compared with 3.39 +/- 1.16 %ID/g (percentage injected dose per gram) for human 89Zr-IgG (P = 0.011) at 168 h and equivalent to ex vivo biodistribution studies. Tracer uptake in other organs was seen primarily in liver and spleen. 89Zr- and 111In-bevacizumab biodistribution was comparable.
Radiolabeled bevacizumab showed higher uptake compared with radiolabeled human IgG in a human SKOV-3 ovarian tumor xenograft. Noninvasive quantitative small-animal PET was similar to invasive ex vivo biodistribution. Radiolabeled bevacizumab is a new tracer for noninvasive in vivo imaging of VEGF in the tumor microenvironment.

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Keywords

111In-bevacizumab biodistribution
 
111In-bevacizumab ex vivo biodistribution
 
72 h onward
 
aspecific control antibody
 
binding studies
 
calculate tumor uptake
 
clear tumor localization
 
ex vivo biodistribution studies
 
microCT images
 
microCT studies
 
neutralizing VEGF
 
Noninvasive quantitative small-animal PET
 
PET isotope 89Zr
 
Radiolabeled bevacizumab
 
radiolabeled human IgG
 
single gamma-emitting isotope 111In
 
Small-animal PET
 
small-animal PET images
 
Vascular endothelial growth factor
 
vivo VEGF visualization