Radiolabeling and biological evaluation of the GX1 and RGD-GX1 peptide sequence for angiogenesis targeting

Autor(es)

Oliveira, E. A. ^[1] ; Faintuch, B. L. ^[1]

Afiliação do(s) autor(es)

^[1] Inst Energy & Nucl Res, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NUCLEAR MEDICINE AND BIOLOGY; v. 42, n. 2, p. 123-130, FEB 2015.
• Citações Web of Science: 6

Resumo

Introduction: Aiming to develop a novel Tc-99m-labeled imaging agent, for angiogenesis and tumor receptors, two peptides obtained from phage display library, namely GXI and the heterodimer RGD-GX1, were synthesized in a cyclic conformation. They were radiolabeled with Tc-99m, employing the HYNIC chelator, for radiochemical evaluation and biological properties. Methods: Radiolabeling, radiochemical control, plasma protein binding, and partition coefficient were assessed for both radioconjugates. Biodistribution in healthy Balb/c mice was carried out, in order to evaluate the biological behaviour of the radiocomplexes. Results: The conjugates displayed a rather similar pharmacokinetic profile. They were prepared with high radiochemical purity (>96%), and both were hydrophilic (log P of -2.25 and -2:51 respectively). Preferential renal excretion was observed. Kidney uptake (4231 +/- 5.35 %ID/g) for Tc-99m-HYNIC-E-1c(RGDfk)-c(GX1)1, 1 h post-injection was about three times higher than the uptake of Tc-99m-HYNIC-PEG(4)-c(GX1) (11.92 +/- 4.77%ID/g). Total blood, bone and muscle values revealed a slightly slower clearance for the RGD-GX1 radiocomplex. Conclusion: The high radiochemical purity achieved, and the similar in vivo profile observed for both radioconjugates, make them potential candidates for radiopharmaceuticals for tumor imaging. Further investigations of binding affinity, and uptake of GXI and RGD-GX1 peptides in tumor models, are warranted. (C) 2014 Elsevier Inc. All rights reserved. (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