title: Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models.
abstract: Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil. ericaoliveira@usp.br.|School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580 Bloco 17, São Paulo, 05508-900, Brazil. ericaoliveira@usp.br.
authors.forename: Érica Aparecida
authors.initials: ÉA
authors.lastname: de Oliveira
authors.affiliation: Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil.
authors.forename: Bluma Linkowski
authors.initials: BL
authors.lastname: Faintuch
authors.affiliation: Laboratory of Biopharmacology in Animal Cells, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo, 05503-900, Brazil.
authors.forename: Roselaine Campos
authors.initials: RC
authors.lastname: Targino
authors.affiliation: Laboratory of Biopharmacology in Animal Cells, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo, 05503-900, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Moro
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Teaching and Research Institute, Hospital Sírio-Libanês, Rua Professor Daher Cutait, 69, Sao Paulo, 01308-060, Brazil.
authors.forename: Raquel Chacon Ruiz
authors.initials: RCR
authors.lastname: Martinez
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Teaching and Research Institute, Hospital Sírio-Libanês, Rua Professor Daher Cutait, 69, Sao Paulo, 01308-060, Brazil.
authors.forename: Rosana Lima
authors.initials: RL
authors.lastname: Pagano
authors.affiliation: Laboratory of Neuromodulation and Experimental Pain, Teaching and Research Institute, Hospital Sírio-Libanês, Rua Professor Daher Cutait, 69, Sao Paulo, 01308-060, Brazil.|Division of Functional Neurosurgery, Institute of Psychiatry of Hospital das Clinicas and Department of Neurology, School of Medicine, University of São Paulo, R. Dr. Ovídio Pires de Campos, 785, São Paulo, 01060-970, Brazil.
authors.forename: Erich Talamoni
authors.initials: ET
authors.lastname: Fonoff
authors.affiliation: Nuclear Medicine Laboratory (LIM 43), Medical School, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, s/nº-Rua 1, Sao Paulo, 05403-900, Brazil.
authors.forename: Camila de Godoi
authors.initials: CG
authors.lastname: Carneiro
authors.affiliation: Nuclear Medicine Laboratory (LIM 43), Medical School, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, s/nº-Rua 1, Sao Paulo, 05403-900, Brazil.
authors.forename: Alexandre Teles
authors.initials: AT
authors.lastname: Garcez
authors.affiliation: Nuclear Medicine Laboratory (LIM 43), Medical School, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, s/nº-Rua 1, Sao Paulo, 05403-900, Brazil.
authors.forename: Daniele de Paula
authors.initials: DP
authors.lastname: Faria
authors.affiliation: Nuclear Medicine Laboratory (LIM 43), Medical School, University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar, s/nº-Rua 1, Sao Paulo, 05403-900, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Buchpiguel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005910:Glioma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D009842:Oligopeptides; D019275:Radiopharmaceuticals; D013667:Technetium; C047981:arginyl-glycyl-aspartic acid
keywords: Angiogenesis; GX1 peptide; Glioma; RGD peptide; Technetium-99m; Tumor