Positron Emission Tomography Imaging In Mice Research Articles

Quantitative PET Imaging of VEGF Receptor Expression

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. 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. 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. 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.