Folate receptor-targeted 19 F MR molecular imaging and proliferation evaluation of lung cancer

J Magn Reson Imaging. 2018 Dec;48(6):1617-1625. doi: 10.1002/jmri.26177. Epub 2018 May 13.

Abstract

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.

Keywords: fluorine-19 magnetic resonance; folate receptor; lung cancer; perfluorocarbon nanoparticles; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Fluorine Radioisotopes / chemistry*
  • Fluorocarbons / chemistry
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Fluorescence
  • Molecular Imaging*
  • Nanoparticles / chemistry*
  • Neoplasm Transplantation
  • Positron Emission Tomography Computed Tomography*
  • Prognosis
  • Radiopharmaceuticals

Substances

  • Fluorine Radioisotopes
  • Fluorocarbons
  • Radiopharmaceuticals