Síntese de ligantes para tecnécio -99m derivado da D-glicose e avaliação como marcador tumoral

Abstract

Cancer is one of the principal causes of death nowadays and there is a restless search for methods for early diagnosis in order to determine the proper treatment and increase the chances of cure. Positron emission tomography (PET), a method based on the radioactive tracer 2-fluoro-2-deoxy-D-glucose ([18F]FDG) is used in nuclear medicine to detect solid tumors. The rationale for the use of [18F]FDG relies in thefact that in the early stage of a solid tumor development the cancer cells usually have accelerated metabolism and, in consequence, enhanced glucose uptake. Nevertheless, widespread use of this method is hampered by its high cost. In the vast majority of conventional nuclear medicine procedures 99mTc is used as the radiotracer, since this radioactive atom has appropriate half-life (6.01 hour), is low g-energy radiator (140 keV) and its cheap and readily available. Thus, there is an increasing search for 99mTc-based complexes for the detections of solid tumors. With these considerations in mind, the synthesis of 4-N-[N3-(benzoylmercaptoacetyl) glicylglicylglicyl]aminophenyl â-D-glucopyranoside (Bz-MAG3-G), a D-glucose derivative was undertaken. Thus, N3-(benzoylmercaptoacetylt)riglycine(Bz-MAG3), a protected form of MAG3, a known complexing agent for 99mTc, and 4- aminophenyl â-D-glucopyranoside, were prepared according to literature procedures. Coupling of Bz-MAG3 with the glucoside in DMF, in the presence of N-(3- dimethylaminopropyl)-N-ethylcarbodiimide (EDAC) was achieved in 32 % yield. Bz-MAG3-G was fully characterized using infrared, RMN 1H and RMN 13C spectrometry. Bz-MAG3 and Bz-MAG3-G were converted, into the corresponding 99mTc complexes for comparative biodistribution studies using male SWISS mice. First, the studies were performed in healthy mice. Different biodistribution patterns were observed forthe two compounds. The 99mTc-MAG3 complex showed a biphasic clearance profile, not shown by the D-glucose-based complex. Next, the biodistribution study of the complexes was performed in mice bearing Ehrlich tumor implanted into the posterior right paw. The concentration of the D-glucose-based complex in the tumor was twofold compared to that of the posterior left paw (control), for all the times measured(5, 30, 120 and 240 minutes). This profile was not observed for 99mTc-MAG3 complex.