Experimental study on the feasibility of MR imaging for tumor-associated macrophages
10.3760/cma.j.issn.1005-1201.2010.07.017
- VernacularTitle:肿瘤相关巨噬细胞MR成像可行性的实验研究
- Author:
Jinhua WANG
;
Honghan GONG
- Publication Type:Journal Article
- Keywords:
Macrophage;
Neoplasms;
Magnetic resonance imaging
- From:
Chinese Journal of Radiology
2010;44(7):753-759
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the feasibility of MR imaging for tumor-associated macrophages. Methods BALB/c mice and BALB/c ( nu/nu) nude mice were randomly divided into 6 groups ( before injection, 6, 24, 48, 72 hours and 7 days after injection) and 5 groups (before injection, 6, 24, 48 and 72 hours after injection) with each group of 3 animals, respectively. Macrophages ( RAW 264. 7) were incubated with HSA-IONPs ( dopamine/HSA coating iron oxide nanoparticle) containing 20 μg Fe/ml for 24 hours. Then, 5 x 106 labeled macrophages were collected and injected into subcutaneous 4T1 tumorbearing BALB/c mice and 22B tumor-bearing nude mice via tail vein. At different time points described above, all animals performed transverse and coronal T2-weighted MR scans using a 7. 0 T MR imaging unit.After sacrifice at different time points, tumor, liver and other organs were removed and processed for histological examination. Cytotoxicity of HSA-IONPs were assayed by MTT test, Statistics analysis adopt SPSS 11.5, the differences among groups were analyzed by one-way ANOVA. The difference was regarded as statistically significant when P <0. 05. Image J 1.42 software was used for the quantitative measurement of MR signal intensity. Results Effective cell labeling was confirmed by Prussian blue staining and transmission electron microscopy (TEM ). Iron uptake of single cell was 6. 19 pg. The mean absorbance values of cells incubated with HSA-IONPs for 24 hours in each group were 1. 95 ±0.19, 1. 82 ±0. 29,2. 10 ±0. 14, 1. 96 ±0. 18, 2. 05 ±0. 27 and 2.17 ±0. 22 respectively at different concentrations (5, 10,20, 40, 80, 160 μg/ml). Compared with that in control group (2. 00 ±0. 07), the absorbance values of cells in each group were not significantly different (F = 1.24,P>0. 05). There was a significant linear positive correlation between the labelled macrophage numbers and MR R2 values (r = 0. 99 ,P < 0. 05). In 4T1 tumor model, significant low signal intensity was found on T2WI surrounding the necrosis and cystic degeneration 6 hours after macrophage injection, with a signal reduction of 59.4%. The signal of tumor parenchyma showed no significant change, with signal reduction of 4. 8%. Irregular low signal ring could be seen at the junction of necrosis and parenchyma area at 24 hours after injection, with a signal reduction of 46. 8% and the signal loss was restored to 96. 8% around the necrosis and cystic degeneration. In 22B tumor model, multiple small scattered foci of low signal intensity were presented on T2WI around the necrosis and cystic degeneration 6 hours after macrophage injection with a signal drop of 46. 8% and reduced at 24 hours. 2, 3 or 7 days after macrophage injection, the morphology and location of low signal intensity were similar to those at 24 hours after injection on T2WI. But the signal intensity gradually decreased. The presence of labelled macrophages imaged by MRI were verified by pathology. Conclusion MRI is feasible for the delineation of tumor-associated macrophages. 24 hours after macrophage injection is the optimal time point for the assessment of macrophage migration and infiltration of tumor on T2WI. MRI can be used to evaluate the perfusion and neovascularization of tumor 6 hours after macrophage injection.
