Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography.
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.
Schnell
Oliver
O
Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany.
Krebs
Bjarne
B
Carlsen
Janette
J
Miederer
Isabelle
I
Goetz
Claudia
C
Goldbrunner
Roland H
RH
Wester
Hans-Jürgen
HJ
Haubner
Roland
R
Pöpperl
Gabriele
G
Holtmannspötter
Markus
M
Kretzschmar
Hans A
HA
Kessler
Horst
H
Tonn
Jörg-Christian
JC
Schwaiger
Markus
M
Beer
Ambros J
AJ
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
D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C423503:fluorogalacto-RGD; D005690:Galactose