RESUMEN

El objetivo del presente trabajo es el estudio biológico y radioquímico de dos análogos de la somatostatina, el péptido RC-160 y el Tyr³-Octreotide (TOC), marcados con ^99mTc por método directo e indirecto usando como quelantes mercapto acetil triglicina (MAG3) e hidrazinonicotinamida (HYNIC) respectivamente.

Se realizó la síntesis del benzoil MAG3-RC-160 y del HYNIC-Tyr³-Octreotide los cuales se marcaron con ^99mTc obteniéndose purezas radioquímicas mayor que 70% y mayor que 95% respectivamente.

Se realizaron biodistribuciones en ratas Wistar normales y los resultados se correlacionaron con los datos cromatográficos y de unión a proteinas, encontrándose que a menor lipofilicidad de los complejos se incrementaba la excreción renal.

Se realizaron ensayos de unión a receptores utilizando como fuente de los mismos membranas de corteza de cerebro de rata.

Los mejores resultados se obtuvieron con el conjugado de HYNIC-TOC marcando con tricina como coligando.

ABSTRACT

The aim of the present work was to study the biological and radiochemical behaviour of two somatostatin analogues, the RC-160 and Tyr³Octreotide(TOC) peptides when labeling with ^99mTc by an indirect method using S-Benzoyl- mercaptoacetyl triglycine (MAG3) and hydrazinonicotinamide (HYNIC) as chelating agents. The synthesis of RC160 with S-Benzoyl MAG3 and TOC with HYNIC, for labeling with ^99mTc are also described. The conjugates were prepared on a small scale and labeled with the radionuclide using tricine as coligands for HYNIC conjugates. Chromatohraphic studies were performed using an HPLC system and radiochemical purities higher than 75% and 95% were obtained respectively. Biodistributions studies in normal Wistar rats were performed and results were correlated with chromatographic and protein binding properties. Lower lipophilicity of the labeled conjugates resulted in a higher renal excretion. HYNIC-TOC complex showed promising results when labeling with ^99mTc using tricine as coligand although higher stability should be found for ternary coligands compared to tricine.

Keywords: somatostatin analogues; labelled Tyr³Octreotide; indirect labeling