Development of PET/MRI imaging probes using facile encapsulation methods with specially designed amphiphiles

Objectives The aim of this study is to develop PET/MRI dual modality imaging probes for better diagnosis images. We modified surface of iron oxide (IO) nanoparticles (NPs) to give multimodality and multi-specificity in one-pot system.

Methods Stearylamine was conjugated with mannose, lactose or NOTA for functionalized amphiphiles. IO NPs were encapsulated with polysorbate 60 and the specially designed amphiphiles. Size distribution and zeta potential were analysed using DLS system. Encapsulated IO was tested their stability in high concentration NaCl solution and human serum condition. Phantom study was performed of final probes to estimate of T2-weighted MR signal and compared with Feridex®. Radioisotope 68Ga was labeled and obtained PET/CT, MRI image in animal. The specific uptake was also confirmed by histopathology study.

Results The sizes of prepared NOTA-IO-Man and NOTA-IO-Lac were 10.49 ± 1.27 and 10.69 ± 1.62 nm, respectively, and did not aggregate or degraded in various harsh conditions. The radiochemical yield of both Ga-68 labeled IO NPs was higher than 99%. The calculated relaxivity coefficient (r2) of mM-1s-1 was higher than Feridex®. Specific uptakes of Ga-68-NOTA-IO-Man in lymph node after subcutaneous injection into footpad and in liver and spleen after intravenous injection into tail vein were confirmed by both PET/CT and MRI images. Ga-68-NOTA-IO-Lac showed only liver uptake. Extracted organs were stained into blue that demonstrated the existence of ferric iron representing uptakes of encapsulated IO NPs in in vivo image.

Conclusions We developed iron oxide based PET/MRI dual imaging probes and obtained specific uptake in lymph node, liver and spleen in both imaging system successfully.

Research Support NRF-2012M2A2A7035853] from the National Research Foundation