title: 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis.
abstract: Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin alpha(v)beta(3) is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled alpha(v)beta(3)-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with (18)F via N-succinimidyl-4-[(18)F]fluorobenzoate through the side-chain epsilon-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[(18)F]fluorobenzoyl-RGD ([(18)F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/micromol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [(18)F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[(18)F]fluorobenzoyl labeled cyclic RGD peptide [(18)F]FB-RGD is a potential tracer for imaging alpha(v)beta(3)-integrin positive tumors in brain and other anatomic locations.
authors.affiliation: PET Imaging Science Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Ryan
authors.initials: R
authors.lastname: Park
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Shahinian
authors.forename: Michel
authors.initials: M
authors.lastname: Tohme
authors.forename: Vazgen
authors.initials: V
authors.lastname: Khankaldyyan
authors.forename: Mohammed H
authors.initials: MH
authors.lastname: Bozorgzadeh
authors.forename: James R
authors.initials: JR
authors.lastname: Bading
authors.forename: Rex
authors.initials: R
authors.lastname: Moats
authors.forename: Walter E
authors.initials: WE
authors.lastname: Laug
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000378:metabolism; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D009842:Oligopeptides / Q000493:pharmacokinetics*; D009928:Organ Specificity; D010865:Pilot Projects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid