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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.

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.

To develop a possible PET blood pool imaging agent, a series 68Ga-dextran carboxylate derivatives were prepared. Dextran carboxylates with different degree of oxidations (DO) were prepared through stepwise dextran oxidation using NaIO4 and CH3COOOH. The products were characterized by FT-IR and GPC, followed by solubility and toxicity tests on Hella cells (viability=98.6, 97.4 and 95.6% for 3 dextran carboxylates with DOs: 8.3, 24.6 and 39.8%, respectively. The products were labeled with 68Ga (radiochemical purity>98%; ITLC) followed by stability tests in final solution as well as in presence of cycteine and human serum. Two stable tracers (DOs; 24.6 and 39.8%) were adminstered intravenously into wild type rat tail vein separately demonstrating suitable retention in circulation as expected from blood pool imaging agents. Liver and spleen also contained activities. The major excretion was through urinary pathway esp. for derivative with DO. 39.8%. Unlike 68Ga-dextran, lungs showed lower uptake. The dextran carboxylate with the highest 39.8% showed the best characteristics for a blood pool agent, though more studies including PET imaging in larger mammals are required.

The possibility of 68Ga-dextran complex formation was analyzed in an HEPES-buffered (pH = 4.5) as well as in an alkaline (pH = 9) solution. The result outlined that the alkaline solution was more efficient to achieve a radiolabeling efficiency of 99% for a 5 mg ml−1 dextran solution (10 min, 90 °C). 68Ga-dextran was stable 88, 71 and 86% after 2 h at storage and toward cysteine solution and human serum, respectively. The highest ROI derived %ID g−1 was found within the lungs, followed by the blood, liver, and bladder. Furthermore, a significant uptake was observed in the cartilage tissue. 68Ga-dextran excreted more by the urinary and less by the biliary pathways.

To be used as a carrier of