Nano-octreotida radiomarcada com tecnécio-99 metaestável como agente diagnóstico de tumor secretor de polipeptídeo pancreático (PPoma)

Abstract

Pancreatic cancer is about to become a cause of cancer death in the world. Among its tumors, there is the Pancreatic Polypeptide-Secreting Tumor of the Distal Pancreas (PPoma). A rare tumor that belongs to the malignancy rate (90%), occurring mainly with bad breath and poor prognosis, with survival rates in 5 years of less than 10%. In the absence of diagnosis, this should be done in an intensive or accidental manner or with mass effect, which causes non-specific abdominal pain due to hepatomegaly or symptoms suggestive of obstruction of the pancreatic or biliary duct. PPoma is classified as a non-functional pancreatic neuroendocrine tumor that overexpresses SSTR 2 (Somatostatin Receptor of subtype 2). Octreotide has a high affinity for SST 2, but its labeling with Technetium-99 meta-stable (99mTc) by direct mode has been shown to be low yield. With the advent of nanotechnology, the problems in the targeting of tumor cells in the production and in the adhesion to the radiopharmaceutical are not favorable agents to those overcome. Thus the present work has as main objective the production of nanorradiopharmaceuticals based on polymeric nanoparticles of polylactic acid(PLA) loaded with Octreotide and radiolabeled with 99mTc to obtain a diagnostic agent of the PPoma. Octreotide was encapsulated in alcohol nanoparticles by the emulsion emulsion method using the PLA polymer and the poly(vinyl alcohol) surfactant (PVA) at 4% concentration of the drug. The characterization of the nanoparticles was performed using the technique of Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS) and the efficiency of the encapsulation of the indirect analysis in the spectrophotometer at 279 nm for the reading of Octreotide. Evaluation of cytotoxicity by the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) at various concentrations of the nanosystem against a human pancreatic carcinoma cell line (MIA Paca-2) SSTR 2 by mimicking the PPoma and by direct method radiolabeled the nanosystem with 99mTc and then determined its yield and radiolabel stability up to 24 hours by paper chromatography using a Whatmam n° 1 paper stationary phase and for a mobile acetone phase. The bioavailability study was used in males of Balb/c induced by the MIA Paca-2 xenograft divided into two groups each with 6 animals for the effect of nanoparticles with and without an Octreotide. The results were as nanoparticles of size around 189 nm, by size as well as by AFM and with Polydispersity Index (PDI) 0.097 corroborating the monodispersive behavior. The efficiency of the Octetotide encapsulation was 60%. As nanoparticles were successfully radiolabeled and stable for 24 hours with 99mTc, demonstrating an excellent induced tumor. The MTT assay corroborated a safety of the nanosystem for the cells. Therefore, the use of 99mTc-labeled PLA/PVA/Octreotide nanoparticles can be used as an image agent for PPoma.