title: Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Bjarne
authors.initials: B
authors.lastname: Krebs
authors.forename: Janette
authors.initials: J
authors.lastname: Carlsen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miederer
authors.forename: Claudia
authors.initials: C
authors.lastname: Goetz
authors.forename: Roland H
authors.initials: RH
authors.lastname: Goldbrunner
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pöpperl
authors.forename: Markus
authors.initials: M
authors.lastname: Holtmannspötter
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D005690:Galactose / Q000031:analogs & derivatives*; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C423503:fluorogalacto-RGD; D005690:Galactose