| Abstract: |
In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of αvβ integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides. Methods: Changes in 68Ga-NODAGAc( RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 αvβ-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce αvβ-positive neovasculature when transplanted into nude mice. Tumor uptake of 68Ga-NODAGA-c(RGDfK) was correlated to microvascular density, vascular morphology, and permeability as well as αvβ integrin expression. Results: Bevacizumab significantly inhibited growth of A-431 tumors and caused a significant reduction in microvascular density and αvβ integrin expression within 7 d after start of therapy. Bevacizumab also caused a normalization of blood vessel morhology and decreased tumor necrosis. However, 68Ga-NODAGA-c(RGDfK) uptake was significantly increased at day 7 of therapy and did not decrease until after 3 wk of treatment. In Fadu xenografts, bevacizumab therapy caused only aminor inhibition of tumor growth and minor changes in 68Ga-NODAGAc( RGDfK) uptake. Conclusion: Uptake of radiolabeled RGD peptides is not necessarily decreased by effective antiangiogenic therapy. Early in the course of therapy a decrease in the expression of αvβ integrins may not be reflected by a decrease in the uptake of RGD peptides. |
