Quantitative PET imaging of VEGF receptor expression.
OBJECTIVE
Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling pathway plays pivotal roles in regulating tumor angiogenesis. Quantitative positron emission tomography (PET) imaging of VEGFR will facilitate the planning of whether, and when, to start anti-angiogenic treatment and enable more robust and effective monitoring of such treatment.


METHODS
VEGF(121) was conjugated with DOTA (1,4,7,10-tetra-azacylododecane N,N',N'',N'''-tetraacetic acid) and then labeled with (64)Cu for PET imaging of mice bearing different-sized human glioblastoma U87MG tumors (n = 15). Western blotting and immunofluorescence staining of tumor tissue was carried out to correlate with/validate the imaging results.


RESULTS
The specific activity of (64)Cu-DOTA-VEGF(121) was 3.2 GBq/mg. The uptake of (64)Cu-DOTA-VEGF(121) in the tumor peaked when the tumor size was about 100-250 mm(3). Both small and large tumors had lower tracer uptake indicating a narrow range of tumor size with high VEGFR-2 expression. All tumors had similarly low VEGFR-1 expression. Most importantly, the tumor uptake value obtained from PET imaging had good linear correlation with the relative tumor tissue VEGFR-2 expression as measured by Western blot, where r (2) equals 0.68 based on the PET uptake at 4 h post-injection. Histology of the frozen tumor tissue corroborates well with the imaging results.


CONCLUSIONS
The tumor uptake of (64)Cu-DOTA-VEGF(121) measured by small-animal PET imaging reflects tumor VEGFR-2 expression level in vivo. Such correlation may facilitate future treatment planning and treatment monitoring of cancer and potentially other angiogenesis-related diseases.
Chen
Kai
K
Department of Radiology and Bio-X Program, Stanford University School of Medicine, CA 94305-5484, USA.
Cai
Weibo
W
Li
Zi-Bo
ZB
Wang
Hui
H
Chen
Xiaoyuan
X
D000818:Animals; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes; D019085:Fluorescent Antibody Technique, Direct; D005909:Glioblastoma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D003301:Copper Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
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