Development of Ga-68 labeled, biotinylated thiosemicarbazone dextran-coated iron oxide nanoparticles as multimodal PET/MRI probe.

Bifunctional biotinylated thiosemicarbazone dextran-coated iron oxide Nanoparticles (NPs) were fabricated. Aldehyde groups of the oxidized dextran-coating layer were utilized to conjugate biotin as a tumor-targeting agent and thiosemicarbazide as a cation chelator on the surface of NPs. The final product was characterized for physicochemical and biological properties. It was compatible with red blood cells and did not change the blood coagulation time. It also showed a significantly enhanced affinity to biotin receptor-positive 4T1 cells compared to non-biotinylated ones. The r2 relaxivity coefficient value of the final product was 110.2 mM-1 s-1. Although biotinylated NPs were easily radiolabeled with Ga-68 at room temperature, the stable radiolabeled NPs were achieved at a higher temperature (60 °C). The radiolabeled NPs were majorly accumulated in the liver and spleen. However, about 5.4% ID/g of the radiolabeled NPs was accumulated within the 4T1 tumor site. Blocking studies was performed by the biotin molecules pre-injection showed uptake reduction in the 4T1 tumor (about 1.1% ID/g). The radiolabeled NPs could be used for the early detection of biotin receptor-positive tumors via PET-MRI.

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.

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.