title: Evaluation of Magnetonanoparticles Conjugated with New Angiogenesis Peptides in Intracranial Glioma Tumors by MRI.
abstract: Angiogenesis plays a critical role in progression of malignant gliomas. The development of glioma-specific labeling molecules that can aid detection and visualization of angiogenesis can help surgical planning and improve treatment outcome. The aim of this study was to evaluate if two peptides (GX1 and RGD-GX1) linked to angiogenesis can be used as an MR-imaging markers of angiogenesis. MR imaging was performed in U87 glioblastoma-bearing NOD-SCID mice at different time points between 15 and 120 min post-injection to visualize particle distribution. GX1 and RGD-GX1 exhibited the highest accumulation in U87 glioblastoma at 120 min post i.v. administration. GX1-conjugated agents lead to higher decrease in transverse relaxation time (T2) (i.e., stronger contrast enhancement) than RGD-GX1-conjugated agents in U87 glioblastoma tumor model. In addition, we tested if U87-IDH1R132mutated cell line had different pattern of GX1 or RGD-GX1 particle accumulation. Responses in U87-IDH1WTfollowed a similar pattern with GX1 contrast agents; however, lower contrast enhancement was observed with RGD-GX1 agents. The specific binding of these peptides to human glioblastoma xenograft in the brain was confirmed by magnetic resonance imaging. The contrast enhancement following injection of magnetonanoparticles conjugated to GX1 peptide matched well with CD31 staining and iron staining.
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes 2242, São Paulo, SP, 05508-000, Brazil. ericaoliveira@usp.br.|School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580 Bloco 17, São Paulo, SP, 05508-900, Brazil. ericaoliveira@usp.br.
authors.forename: Erica Aparecida
authors.initials: EA
authors.lastname: de Oliveira
authors.affiliation: Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Jelena
authors.initials: J
authors.lastname: Lazovic
authors.affiliation: Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Horacio
authors.initials: H
authors.lastname: Soto
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes 2242, São Paulo, SP, 05508-000, Brazil.
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.affiliation: Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen school of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Massoud
authors.initials: M
authors.lastname: Akhtari
authors.affiliation: Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Pope
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D005910:Glioma / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid
keywords: Angiogenesis; GX1 peptide; Glioma; MRI; RGD-GX1 peptide