Abstract
Folate receptors (FRs) hold great potential as important diagnostic and prognostic biological marker for cancer. To assess the targeted capability of the FR-targeted perfluorocarbon (PFC) nanoparticles and to assess in vivo the relationship between FR expression and tumor proliferation with fluorine-19 (19 F) MR molecular imaging. Prospective animal cancer model. H460 (n = 14) and A549 (n = 14) nude mice subcutaneous tumor models. 9.4T, 1 H and 19 F RARE sequences. Intracellular uptake of the PFC nanoparticles was tested in H460 and A549 cell lines. 19 F MRI of H460 and A549 subcutaneous tumors was performed following intravenous injection of PFC nanoparticles. The concentration of PFC in tumors were compared. 3'-Deoxy-3'-18 F-fluorothymidine (18 F-FLT) positron emission tomography / computed tomography (PET/CT) imaging, Ki-67, and proliferating cell nuclear antigen (PCNA) staining were performed to confirm tumor proliferation. One-way or two-way analysis of variance. P < 0.05 was considered a significant difference. The diameter of the FR-targeted nanoparticles was 108.8 ± 0.56 nm, and the zeta potential was -58.4 ± 10.8 mV. H460 cells incubated with FR-targeted nanoparticles showed ∼59.87 ± 3.91% nanoparticles-labeled, which is significantly higher than the other groups (P < 0.001). The PFC concentration in H460 tumors after injection with FR-targeted nanoparticles was 4.64 ± 1.21, 8.04 ± 1.38, and 9.16 ± 2.56 mmol/L at 8 hours, 24 hours, and 48 hours, respectively (P < 0.05 compared to others). The ratio of 18 F-FLT uptake for H460 and A549 tumors was 3.32 ± 0.17 and 1.48 ± 0.09 (P < 0.05), and there was more Ki-67 and PCNA in H460 tumor than A549. DATA CONCLUSION: 19 F MRI with FR-targeted PFC nanoparticles can be used in differentiating of FR-positive and FR-negative tumors, and further, in evaluation of the two cancer models proliferation. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1617-1625.
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