Synthesis, characterization, and in vitro and in vivo 68Ga radiolabeling of thiosemicarbazone Schiff base derived from dialdehyde dextran as a promising blood pool imaging agent

• Published in: International journal of biological macromolecules Vol. 125; pp. 915 - 921
• Main Authors: Almasi, Tinoosh, Jabbari, Keyvan, Gholipour, Nazila, Mokhtari Kheirabadi, Amin, Beiki, Davood, Shahrokhi, Pejman, Akhlaghi, Mehdi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.03.2019
• Subjects: Blood pool imaging agent; Cytotoxicity; Radiolabeling; Thiosemicarbazone dialdehyde dextran; Radiolabeling; Cytotoxicity; Blood pool imaging agent; Thiosemicarbazone dialdehyde dextran
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2018.12.133

To be used as a carrier of 68Ga radioisotope for possible blood pool imaging studies, dialdehyde dextran thiosemicarbazone (DADTSC) Schiff base polymer with different thiosemicarbazone contents (TSCC) = 0.93, 2.43, and 3.4 mmol/g were synthesized and characterized by FT-IR, GPC, and CHNS. Although they were successfully radiolabeled at room temperature, stable radio-complexes were prepared at 60 °C. Effect of thiosemicarbazone content on the dissolution rate, cytotoxicity, coagulation and hemolysis activities, and radiolabeling efficiency of Schiff bases as well as on the in-vitro radio-complexes stability was investigated. DADTSC1 (TSCC = 0.93 mmol/g) showed a less cytotoxicity (cell viability, CV50 = 490 μg/ml), a better solubility, suitable coagulation and hemolytic activities, and a sufficient radiolabeling efficiency (Radiochemical purity (RCP) > 95%) and formed a stable (RCP > 90%) radio-complex, which be chosen for in-vivo biodistribution study in healthy rats through tissue sampling and counting for radioactivity. Like blood pool imaging agents, 68Ga-DADTSC1 presented a retention profile in blood circulation, though more studies, including imaging in larger mammals, are required. [Display omitted] •Dialdehyde dextran thiosemicarbazone (DADTSC) was synthesized with three different thiosemicarbazone contents (TSCC).•Effect of TSCC on the cytotoxicity, solubility, coagulation and hemolysis activities, and radiolabeling yield was studied.•DADTSC1 (TSCC = 0.93 mmol/g) showed a less cytotoxicity, a better solubility and a sufficient radiolabeling efficiency.•68Ga-DADTSC1 presented a long retention of administrated radioactivity in the blood indicates its blood pool agent value.