title: Comparison of Ga-68-Labeled Fusarinine C-Based Multivalent RGD Conjugates and [(68)Ga]NODAGA-RGD-In Vivo Imaging Studies in Human Xenograft Tumors.
abstract: Multimeric arginine-glycine-aspartic acid (RGD) peptides have advantages for imaging integrin αvβ3 expression. Here, we compared the in vitro and in vivo behavior of three different Ga-68-labeled multimeric Fusarinine C-RGD (FSC-RGD) conjugates, whereby RGD was coupled directly, via a succinic acid or PEG linker (FSC(RGDfE)3, FSC(succ-RGD)3, FSC(Mal-RGD)3). The positron emission tomography/X-ray computed tomography (PET/CT) imaging properties were further compared using [(68)Ga]FSC(succ-RGD)3 with the monomeric [(68)Ga]NODAGA-RGD in a murine tumor model.
  
  
  
  FSC-RGD conjugates were labeled with Ga-68, and stability properties were studied. For in vitro characterization, the partition coefficient, integrin αvβ3 binding affinity, and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET/CT were carried out using mice bearing either human M21/M21-L melanoma or human U87MG glioblastoma tumor xenografts.
  
  
  
  All FSC-RGD conjugates were quantitatively labeled with Ga-68 within 10 min at RT. The [(68)Ga]FSC-RGD conjugates exhibited high stability and hydrophilic character, with only minor differences between the different conjugates. In vitro and in vivo studies showed enhanced integrin αvβ3 binding affinity, receptor-selective tumor uptake, and rapid renal excretion resulting in good imaging properties.
  
  
  
  The type of linker between FSC and RGD had no pronounced effect on targeting properties of [(68)Ga]FSC-RGD trimers. In particular, [(68)Ga]FSC(succ-RGD)3 exhibited improved properties compared to [(68)Ga]NODAGA-RGD, making it an alternative for imaging integrin αvβ3 expression.
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.|Department of Nuclear Medicine, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Chuangyan
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Gerben M
authors.initials: GM
authors.lastname: Franssen
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Milos
authors.initials: M
authors.lastname: Petrik
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Laverman
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Summer
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rangger
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Haubner
authors.affiliation: Division of Molecular Biology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
authors.affiliation: Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria. Clemens.Decristoforo@tirol-kliniken.at.
authors.forename: Clemens
authors.initials: C
authors.lastname: Decristoforo
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D008545:Melanoma / Q000000981:diagnostic imaging / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry*; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: C572723:1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane; D000085:Acetates; D005290:Ferric Compounds; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D006877:Hydroxamic Acids; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C010966:fusigen; C047981:arginyl-glycyl-aspartic acid
keywords: Fusarinine C; Gallium-68; Integrins; Positron emission tomography (PET); RGD peptides