Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models

Autor(es):Mostrar menos -

de Oliveira, Erica Aparecida ^{[1, 2]} ; Faintuch, Bluma Linkowski ^[1] ; Targino, Roselaine Campos ^[3] ; Moro, Ana Maria ^[3] ; Ruiz Martinez, Raquel Chacon ^[4] ; Pagano, Rosana Lima ^[4] ; Fonoff, Erich Talamoni ^{[4, 5, 6]} ; Carneiro, Camila de Godoi ^[7] ; Garcez, Alexandre Teles ^[7] ; Faria, Daniele de Paula ^[7] ; Buchpiguel, Carlos Alberto ^[7]

Afiliação do(s) autor(es)

^[1] Inst Energy & Nucl Res, Radiopharm Ctr, Av Prof Lineu Prestes 2242, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Av Prof Lineu Prestes 580, Bloco 17, BR-05508900 Sao Paulo - Brazil

^[3] Butantan Inst, Lab Biopharmacol Anim Cells, Av Vital Brasil, BR-05503900 Sao Paulo - Brazil

^[4] Hosp Sirio Libanes, Teaching & Res Inst, Lab Neuromodulat & Expt Pain, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Div Funct Neurosurg, Inst Psychiat, Hosp Clin, R Dr Ovidio Pires de Campos 785, BR-01060970 Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sch Med, Dept Neurol, R Dr Ovidio Pires de Campos 785, BR-01060970 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Sch Med, Nucl Med Lab LIM 43, Av Dr Eneas de Carvalho Aguiar, S Rua 1, BR-05403900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Amino Acids; v. 48, n. 3, p. 821-831, MAR 2016.
• Citações Web of Science: 6

Resumo

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 +/- A 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 +/- A 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 Tc-99m-HYNIC-E-{[}c(RGDfk)-c(GX1)] were successful, and better than with Tc-99m-HYNIC-PEG(4)-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended. (AU)

• Processo FAPESP: 11/12405-0 - Desenvolvimento de radiotraçadores angiogênicos para diagnóstico de glioma: estudo em modelo animal
• Beneficiário: Érica Aparecida de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado