In vivo "hot spot" MR imaging of neural stem cells using fluorinated nanoparticles

To optimize ¹⁹F MR tracking of stem cells, we compared cellular internalization of cationic and anionic perfluoro-15-crown-5-ether (PFCE) nanoparticles using cell culture plates with different surface coatings. The viability and proliferation of anionic and cationic PFCE-labeled neural stem cells (NSCs) did not differ from unlabeled cells. Cationic PFCE nanoparticles (¹⁹F T1/T2 = 580/ 536 ms at 9.4 Tesla) were superior to anionic particles for intracellular fluorination. Best results were obtained with modified polystyrene culture dishes coated with both carboxylic and amino groups rather than conventional carboxyl-coated dishes. After injecting PFCE-labeled NSCs into the striatum of mouse brain, cells were readily identified in vivo by ¹⁹F MRI without changes in signal or viability over a 2-week period after grafting. These results demonstrate that neural stem cells can be efficiently fluorinated with cationic PFCE nanoparticles without using transfection agents and visualized in vivo over prolonged periods with an MR sensitivity of approximately 140 pmol of PFCE/cell.