Inhibitors targeting the
integrin alpha(v)beta(3) are promising new agents currently tested in clinical trials for supplemental
therapy of
glioblastoma multiforme (GBM). The aim of our study was to evaluate (18)F-labeled glycosylated
Arg-Gly-Asp peptide ([(18)F]Galacto-RGD) PET for noninvasive imaging of alpha(v)beta(3) expression in patients with GBM, suggesting eligibility for this kind of additional treatment. Patients with suspected or recurrent GBM were examined with [(18)F]Galacto-RGD PET. Standardized uptake values (SUVs) of
tumor hotspots, galea, and blood pool were derived by region-of-interest analysis. [(18)F]Galacto-RGD PET images were fused with cranial MR images for
image-guided surgery.
Tumor samples taken from areas with intense tracer accumulation in the [(18)F]Galacto-RGD PET images and were analyzed histologically and immunohistochemically for alpha(v)
beta(3) integrin expression. While normal brain tissue did not show significant tracer accumulation (mean SUV, 0.09 +/- 0.04), GBMs demonstrated significant but heterogeneous tracer uptake, with a maximum in the highly proliferating and infiltrating areas of
tumors (mean SUV, 1.6 +/- 0.5). Immunohistochemical staining was prominent in
tumor microvessels as well as glial
tumor cells. In areas of highly proliferating glial
tumor cells, tracer uptake (SUVs) in the [(18)F]Galacto-RGD PET images correlated with immunohistochemical alpha(v)
beta(3) integrin expression of corresponding
tumor samples. These data suggest that [(18)F] Galacto-RGD PET successfully identifies alpha(v)beta(3) expression in patients with GBM and might be a promising tool for planning and monitoring individualized
cancer therapies targeting this
integrin.