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Folate receptor‐targeted 19 F MR molecular imaging and proliferation evaluation of lung cancer
Author(s) -
Xu Xiuan,
Yan Yuling,
Liu Fang,
Wu Lina,
Shao Mengping,
Wang Kai,
Sun Xilin,
Li Yingbo,
Beinpuo Ernest Sanyare Warmann,
Shen Baozhong
Publication year - 2018
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.26177
Subject(s) - folate receptor , in vivo , lung cancer , proliferating cell nuclear antigen , positron emission tomography , a549 cell , targeted therapy , chemistry , receptor , cell growth , nuclear medicine , cancer , cancer research , medicine , microbiology and biotechnology , pathology , immunohistochemistry , cancer cell , biology , biochemistry
Background Folate receptors (FRs) hold great potential as important diagnostic and prognostic biological marker for cancer. Purpose 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. Study Type Prospective animal cancer model. Animal Model H460 ( n = 14) and A549 ( n = 14) nude mice subcutaneous tumor models. Field Strength 9.4T, 1 H and 19 F RARE sequences. Assessment 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. Statistical Tests One‐way or two‐way analysis of variance. P < 0.05 was considered a significant difference. Results 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. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1617–1625