Emprego do complexo 99mTc - HYNIC - Bombesina (7-14) livre e encapsulado em lipossomas na identificação de tumores em modelos experimentais

Abstract

Breast cancer is one of the most common tumors in women, showing high levels of mortality. Thus, many efforts have been made to produce diagnostic techniques that can assist in the treatment, increasing the chances of cure of the patients. Over the past years, radiolabeledpeptides for diagnosis and/or therapy has gained enormous interest due to the over expression of receptors for those peptides on the surface of cancer cells. Bombesin (BBN) is a tetradecapeptide, isolated from a frog, which binds specifically to receptors for gastrin releasing peptide (GRP). A variety of tumors have been found to express receptors for this peptide, such as lung, prostate, and breast. Therefore, radiolabeled BBN analogs with a high affinity for these receptors might be used for scintigraphic imaging of these tumor types. Technetium-99m has been mostly used for labeling radiopharmaceuticals due to its suitable characteristics, such ashalf-live (6.02 hours), gamma emission in low energy (140 keV), and inexpensive isotope cost. 2-Hydrazinonicotinamide (HYNIC) is an attractive bifunctional chelating ligand for preparing 99mTc-labeled peptides, because it shows a high labeling efficiency. Liposomes are spherical vesicles that form when phospholipids are exposed to an aqueous environment. These vesicles can be used to deliver substances to specific tissues, including tumors. In this sense, longcirculating,pH-sensitive liposomes show high selectivity to tumor due to their instability toward areas of lower pH, such as inflammation, infection and tumors. This work reported the technetium-99m labeling of a bombesin derivative (HYNIC-bAla-bombesina(7-14)). In addition, the radiolabeled peptide, free or encapsulated into long-circulating pH-sensitive liposomes, was evaluated regarding its ability to identify Ehrlich tumor and MDA-MB-231 tumor in animal models. Results obtained from this work showed high specificity to tumors tested. As a result,target/non-target ratios were higher than 1.5 during the whole experiment. These findings, suggest that 99mTc-HYNIC-bAla-bombesina(7-14) can be used to identify those tumors.