Noninvasive visualization of the activated αvβ3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD

Background The integrin alpha v beta 3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of alpha v beta 3 expression. We developed [F-18]Galacto-RGD, a F-18-labeled glycosylated alpha v beta 3 antagonist, allowing monitoring of alpha v beta 3 expression with positron emission tomography (PET). Methods and Findings Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [F-18]Galacto-RGD in the tumor correlates with alpha v beta 3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize alpha v beta 3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [F-18]Galacto-RGD with PET enables noninvasive quantitative assessment of the alpha v beta 3 expression pattern on tumor and endothelial cells in patients with malignant tumors. Conclusions Molecular imaging with [F-18]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the alpha v beta 3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.