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

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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 99mTc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with 99mTc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.

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Acknowledgments

The authors are grateful to Ana Funari, Aryel Heitor and Daniele Seo for the assistance during some experiments.

Author information

Author notes

  1. Érica Aparecida de Oliveira

    Present address: School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580 Bloco 17, São Paulo, 05508-900, Brazil

Authors and Affiliations

  1. Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil

    Érica Aparecida de Oliveira & Bluma Linkowski Faintuch

  2. Laboratory of Biopharmacology in Animal Cells, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo, 05503-900, Brazil

    Roselaine Campos Targino & Ana Maria Moro

  3. Laboratory of Neuromodulation and Experimental Pain, Teaching and Research Institute, Hospital Sírio-Libanês, Rua Professor Daher Cutait, 69, Sao Paulo, 01308-060, Brazil

    Raquel Chacon Ruiz Martinez, Rosana Lima Pagano & Erich Talamoni Fonoff

  4. 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

    Erich Talamoni Fonoff

  5. 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

    Camila de Godoi Carneiro, Alexandre Teles Garcez, Daniele de Paula Faria & Carlos Alberto Buchpiguel

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  1. Érica Aparecida de Oliveira
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  2. Bluma Linkowski Faintuch
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  3. Roselaine Campos Targino
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  4. Ana Maria Moro
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  8. Camila de Godoi Carneiro
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  11. Carlos Alberto Buchpiguel
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Corresponding author

Correspondence to Érica Aparecida de Oliveira.

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The authors declare that they have no conflict of interest.

Funding

Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil [Fapesp 2011/12405-0].

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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de Oliveira, É.A., Faintuch, B.L., Targino, R.C. et al. Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models. Amino Acids 48, 821–831 (2016). https://doi.org/10.1007/s00726-015-2130-y

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  • DOI: https://doi.org/10.1007/s00726-015-2130-y

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