Radiochemical and biological properties of peptides designed to interact with EGF receptor: Relevance for glioblastoma

Radiolabeled peptides with high specificity to receptors expressed on tumor cells hold a great promise as diagnostic and therapeutic tracers. The main objective of this study was to evaluate the radiochemical and biological properties of two [131I]I-peptides, as well as their interaction with the epidermal growth factor receptor (EGFR), overexpressed in a wide variety of tumors, including glioblastoma. The EEEEYFELV peptide and its analogue DEDEYFELV, both designed to interact with EGFR, were chemically synthesized, purified and radiolabeled with iodine-131 ([131I]NaI). The radioiodination was evaluated and optimized using the chloramine-T methodology. The stability, serum proteins binding and partition coefficient were assessed for both radioconjugates. Moreover, the binding and internalization of synthesized radiopeptides with rat glioblastoma cells (C6) and with rat brain homogenates from a glioblastoma induced model were evaluated and ex vivo biodistribution studies were performed. Under optimized radiolabeling conditions, the peptides showed an average radiochemical yield of 90–95%. The stability studies showed that both peptides were stable up to 24 h in reaction medium, saline, and human serum. Furthermore, [131I]I-peptides have hydrophilic features and showed binding percentage to serum proteins of around 50%, which is highly compatible with clinical applications. Moreover, the radiopeptides presented capacity for binding and internalization in both tumor cells (C6) and rat brain tissues after tumor induction. Biodistribution studies corroborated the cell culture studies and confirmed the different binding characteristics derived from a simple change of two amino acids (Glu ➔ Asp1,3) in their sequences. The results obtained are consistent enough to motivate further studies. Thereby, these radiolabeled peptides might be useful for diagnostic applications.