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Quantitative PET imaging of VEGF receptor expression

¹ Radiology, Stanford University, Stanford, California

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Objectives: VEGF/VEGFR signaling pathway plays pivotal roles in regulating tumor angiogenesis. Since VEGFR expression is highly dynamic during tumor progression, quantitative 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: VEGF₁₂₁ was conjugated with DOTA and labeled with ⁶⁴Cu for PET imaging of mice bearing different sized human glioblastoma U87MG tumors (n = 15). Western blotting of tumor tissue lysate was performed to correlate the VEGFR expression level with ⁶⁴Cu-DOTA-VEGF₁₂₁ uptake in the tumors. Immunofluorescence staining was also carried out to validate the imaging results.

Results: The specific activity of ⁶⁴Cu-DOTA-VEGF₁₂₁ was 3.2 ± 0.1 GBq/mg with radiochemical purity of >98%. The uptake of ⁶⁴Cu-DOTA-VEGF₁₂₁ in the tumor peaked when the tumor size was about 100-200 mm³ during the exponential growth phase. Both small and large tumors had lower tracer uptake indicating that the window with high VEGFR expression was quite narrow. Immunofluorescence staining revealed that the tumor had minimal VEGFR-1 expression while the VEGFR-2 expression level is quite different. Most importantly, the tumor uptake value obtained from PET imaging had good linear correlation with the relative tumor tissue VEGFR-2 expression (r² = 0.68 based on 4 h time point PET quantification).

Conclusions: The tumor uptake of ⁶⁴Cu-DOTA-VEGF₁₂₁ measured by microPET imaging reflects tumor VEGFR-2 expression level in vivo. This is, to our knowledge, the first report of quantitative PET imaging of VEGFR-2 in living subjects. Such correlation is critical for future treatment planning and treatment monitoring applications in both cancer and other angiogenesis-related diseases.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, K. Articles by Chen, X. PubMed Articles by Chen, K. Articles by Chen, X.