Synthesis and biological evaluation of 125I-erythropoietin as a potential radiopharmaceutical agent for tumours

• Published in: Brazilian Journal of Pharmaceutical Sciences Vol. 47; no. 1; pp. 83 - 88
• Main Authors: Clemente, Gonçalo dos Santos, Duarte, Vera Lúcia Serra
• Format: Journal Article
• Language: English; Portuguese
• Published: Universidade de São Paulo, Faculdade de Ciências Farmacêuticas 01-03-2011; Universidade de São Paulo
• Subjects: 125I-erythropoietin; EPO expressive tumours; Eritropoese; Eritropoetina; Erythropoiesis; Erythropoietin (EPO); Glycoprotein hormone; Hormônio glicoprotéico; Iodine-125; Iodo-125; PHARMACOLOGY & PHARMACY; Radiopharmaceuticals; Tumores expressores de EPO; Erythropoiesis; Eritropoese; Iodine-125; Hormônio glicoprotéico; Tumores expressores de EPO; 125I-erythropoietin; Iodo-125; Erythropoietin (EPO); EPO expressive tumours; Glycoprotein hormone; Radiopharmaceuticals; Eritropoetina
• ISSN: 2175-9790; 1984-8250; 2175-9790
• DOI: 10.1590/S1984-82502011000100010

Erythropoietin (EPO) is a glycoprotein hormone responsible for regulating erythropoiesis. Expression of EPO and EPO receptors (EPOr) has recently been demonstrated in some neoplastic cell lines and tumours, suggesting a potential new target for therapy. In this work, EPO was labeled with iodine-125 using the lactoperoxidase method, known to prevent damage to protein during radioiodination, and labeling conditions were optimized. In vitro stability studies have shown that 125I-EPO is radiochemically stable for 20 days after radiolabeling. In vitro cell binding studies have demonstrated very low binding (<2%) of EPO to normal and neoplastic cell lines tested. As expected, the biodistribution in healthy mice exhibited comparatively high rates of fixation in the organs of the excretory system. Thyroid also proved to be a critical organ which may indicate in vivo dissociation of 125I-EPO. In mice with induced melanoma, only a residual fixation in the tumour was evident. Further studies are warranted on other tumoral cell lines to better understand the binding process and internalization into cells. Studies on EPO labeled with carbon-11 could be valuable, since there is a greater chance of preserving the biological activity of the protein using this method.