VIII International Symposium on Chemistry and Pharmaceutical Sciences

SICF

VIII Symposium "Design, Obtaining and Development of Drugs"

Ubiquicidin 29-41 fragment labeled with 99mTc as a radiopharmaceutical for the study of infections.

Abstract

The labeled fragment 29-41 of Ubiquicidin (UBI29-41) has been useful for the study of active infection. Objective: Develop a formulation for 99mTc labeling of UBI29-41 synthesized in Cuba. MATERIALS AND METHODS: UBI29-41 (TGRAKRRMQYNRR) was obtained by solid phase synthesis using Fmoc/tBu chemistry, and functionalized MBHA resin. Labeling with 99mTc was carried out directly: 200 µL (10-20 µg) of SnCl2*2H2O, 1 mL of [99mTc]NaTcO4 solution (740-925 MBq) were added to 50 µg of UBI29-41 (100µL). ) and 30 µL of 0.1 mol/L NaOH, incubating for 15 min at room temperature. Radiochemical purity (RQP) was established as a quality parameter. Stability was determined at room temperature for up to 24 h in physiological saline solution (PSS) at different pH values and incubating in blood serum. RESULTS: The crude peptide was obtained, directly from the synthesis, with 85.97% purity, which increased to 99.15% after purification by semipreparative HPLC-RP. With the formulation containing 50 µg of UBI29-41 + 15 µg of SnCl2*2H2O and 30 µL of 0.1 mol/L NaOH, RQP results of [99mTc]Tc-UBI29-41 greater than 95% were obtained. The stability results in PSS at pH = 7 and 9 and in blood serum did not show significant differences in RQP in the first 4 h, and only decreased by approximately 2% after 24 h post-labeling. CONCLUSIONS: The UBI29-41 peptide was synthesized in solid phase and a formulation was obtained for its satisfactory labeling with 99mTc.

Resumen

El fragmento 29-41 de la Ubiquicidina (UBI29-41) marcado ha resultado útil para el estudio de infección activa. Objetivo: Desarrollar una formulación para la marcación con 99mTc de la UBI29-41 sintetizada en Cuba. MATERIALES Y MÉTODOS: La UBI29-41 (TGRAKRRMQYNRR) se obtuvo mediante síntesis en fase sólida empleando la química Fmoc/tBu, y resina MBHA funcionalizada. La marcación con 99mTc se realizó por vía directa: a 50 µg de UBI29-41 (100µL) se le adicionaron 200 µL (10-20 µg) de SnCl2*2H2O, 1 mL de disolución de [99mTc]NaTcO4 (740-925 MBq) y 30 µL de NaOH 0,1 mol/L incubando 15 min a temperatura ambiente. La pureza radioquímica (PRQ) se estableció como parámetro de calidad. Se determinó la estabilidad a temperatura ambiente hasta 24 h en disolución salina fisiológica (SSF) a diferentes valores de pH e incubando en suero sanguíneo. RESULTADOS: El péptido crudo se obtuvo, directamente de la síntesis, con 85,97% de pureza, que aumentó hasta 99,15% después de su purificación mediante HPLC-RP semipreparativa. Con la formulación que contenía 50 µg de UBI29-41 + 15 µg de SnCl2*2H2O y 30 µL de NaOH 0,1 mol/L, se obtuvieron resultados de PRQ de [99mTc]Tc-UBI29-41 superiores al 95%. Los resultados de estabilidad en SSF a pH= 7 y 9 y en suero sanguíneo, no mostraron diferencias significativas de PRQ en las primeras 4 h, y solo disminuyeron en aproximadamente 2%, transcurridas 24 h posmarcación. CONCLUSIONES: Se sintetizó en fase sólida el péptido UBI29-41 y se obtuvo una formulación para su marcación satisfactoria con 99mTc.