The MRI study of supraparamagnetic ironic oxide loaded polymeric nano-vesicles in human colonic carcinoma xenograft in nude mice (2011)

Objective To synthesize the hydrophobic supraparamagnetic ironic oxide(SPIO) loaded and hydrophilic SPIO loaded polymeric nano-vesicles and to investigate the feasibility of using hydrophobic SPIO loaded and hydrophilic SPIO loaded polymeric nano-vesicles to display the tumor in MRI in vivo through animal experiments. Methods The polymeric nano-vesicles were prepared from poly (D, L-lactic acid) (PDLLA) and poly (ethylene glycol) (PEG) by a multiple emulsion/solvent evaporation method.The hydrophobic SPIO and hydrophilic SPIO were loaded in the polymeric nano-vesicles respectively.Eighteen nude mice models with human colorectal carcinoma xenograft were established. They were divided equally into three groups (n = 6). The three groups of nude mice models were injected with water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle via the mice caudal vein respectively.Dynamic MRI scan were performed in all the mice models. T2WI signal intensity and T2 relaxation time were measured in the tumor, liver and muscle by using T2 mapping software. ANOVA of repeated measurement was used to analyze if there were significant differences of signal intensity changes among the three groups, while Bonferroni method was used for pair-wise comparison. Results On T2 WI, tumors showed decrease in signal intensity after hydrophobic or hydrophilic SPIO loaded polymeric nano-vesicle injection, while no signal intensity decrease was found in the tumor after water-soluble SPIO administration. The maximum percentage of signal intensity decrease in tumor caused by hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 11.00%, 11.40%, respectively. There was statistical significant difference of signal intensity changes among these three groups (F = 10. 96, P ＜ 0. 01). The decrease in signal intensity in the groups with hydrophilic or hydrophobic SPIO loaded polymeric nano-vesicles injection were more pronounced as compared with that of water-soluble SPIO (P ＜ 0. 05), but there was no significant difference in signal intensity decrease between the groups of hydrophilic and hydrophobic SPIO-loaded polymeric vesicles injection (P ＞0. 05). The three agents could lead to signal intensity decrease in the liver. The maximum percentage of signal intensity decrease in liver caused by water-soluble SPIO, hydrophobic SPIO loaded and hydrophilic SPIO loaded vesicle were 32. 85%, 52. 77%, 56. 89%, respectively. There was statistical significant difference between these groups (F = 161.18, P ＜ 0. 01) . The groups of injecting hydrophilic and hydrophobic SPIO loaded polymeric nano-vesicles had the more obvious signal decrease than the one with water-soluble SPIO (P ＜ 0. 01). Hydrophilic SPIO loaded polymeric nano-vesicles exhibited more signal intensity decrease than hydrophobic SPIO loaded polymeric nano-vesicles (P ＜ 0. 01). All three agents could not lead to T2WI signal decrease in the muscle, and there was no significant difference in signal change on T2 WI among three groups (F = 0. 59, P ＞ 0. 05). Conclusion SPIO loaded polymeric nano-vesicles can cause significant T2WI signal loss in human colonic carcinoma on MR imaging in vivo. It can be used as tumor imaging contrast agents.

Key words: 
Magnetic resonance imaging; Colon neoplasms; Animal experimentation